Information on EC 2.1.1.28 - phenylethanolamine N-methyltransferase

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The expected taxonomic range for this enzyme is: Euteleostomi

EC NUMBER
COMMENTARY
2.1.1.28
-
RECOMMENDED NAME
GeneOntology No.
phenylethanolamine N-methyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + phenylethanolamine = S-adenosyl-L-homocysteine + N-methylphenylethanolamine
show the reaction diagram
random binding mechanism with a kinetically preferred order of binding where S-adenosyl-L-methionine is the preferred first substrate
-
S-adenosyl-L-methionine + phenylethanolamine = S-adenosyl-L-homocysteine + N-methylphenylethanolamine
show the reaction diagram
ordered sequential reaction
-
S-adenosyl-L-methionine + phenylethanolamine = S-adenosyl-L-homocysteine + N-methylphenylethanolamine
show the reaction diagram
to elucidate the detailed mechanism of enzymatic catalysis of PNMT, combined quantum-mechanical/molecular-mechanical (QM/MM) calculations are performed. The calculation results reveal that this catalysis contains three elementary steps: the deprotonation of protonated norepinphrine, the methyl transferring step and deprotonation of the methylated norepinphrine. The methyl transferring step is proved to be the rate-determining step undergoing a SN2 mechanism with an energy barrier of 16.4 kcal/mol
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
methyl group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
catecholamine biosynthesis
-
-
catecholamine biosynthesis
-
-
Metabolic pathways
-
-
noradrenaline and adrenaline degradation
-
-
Tyrosine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase
Acts on various phenylethanolamines; converts noradrenaline into adrenaline.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
methyltransferase, noradrenaline N-
-
-
-
-
NMT
-
-
-
-
noradrenalin methyltransferase
-
-
-
-
noradrenalin N-methyltransferase
-
-
-
-
noradrenaline N-methyltransferase
-
-
-
-
norepinephrin N-methyltransferase
-
-
-
-
norepinephrine methyltransferase
-
-
-
-
norepinephrine N-methyltransferase
-
-
-
-
phenethanolamine methyltransferase
-
-
-
-
phenethanolamine N-methyltransferase
-
-
-
-
PNMT
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9037-68-7
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
21 male and 1 female patient at 0-12 years after heart transplantation, mean age 45.7 years: During the first years after heart transplantation, phenylethanolamine N-methyltransferase mRNA levels are relatively high compared with later years. There is a correlation of phenylethanolamine N-methyltransferase mRNA with years elapsed form heart transplantation (r = -0.56). There is a negative linear correlation between phenylethanolamine N-methyltransferase mRNA and the low frequency band of the power spectrum (r = - 0.47).
-
-
Manually annotated by BRENDA team
expression plasmid pET17PNMT-his
Uniprot
Manually annotated by BRENDA team
female Japanese woman, gene PNMT
-
-
Manually annotated by BRENDA team
immunohistochemical analysis in normal human medulla shows a expression of phenylethanolamine N-methyltransferase localized to the cytoplasm. All tyrosine hydroxylase-positive cells contain phenylethanolamine N-methyltransferase. All normal human chromaffin cells also strongly express noradrenaline transporter, which is always colocalized with phenylethanolamine N-methyltransferase. Double-labeling experiments on phaeochromocytoma tissue reveals, that the expression of phenylethanolamine N-methyltransferase is variable, ranging from strong to weak to absent. The immunohistochemical detection of phenylethanolamine N-methyltransferase correlates with the presence of adrenaline in all but one sample (but the intensitiy levels do not correlate). In human phaeochromocytomas the expression of the noradrenaline transporter is not consistently co-localized with phenylethanolamine N-methyltransferase.
-
-
Manually annotated by BRENDA team
recombinant enzyme; recombinant enzyme with C-terminal His6 tag
-
-
Manually annotated by BRENDA team
the phenylethanolamine N-methyltransferase inhibitory potency of 3-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline is lower than the of other 1,2,3,4-tetrahydroisoquinolines, some of them show good selectivity due to their extremely low alpha2-adrenoceptor affinity
-
-
Manually annotated by BRENDA team
; mouse pheochromocytoma cell lines 862L and 10/9CRC1 from tumors arising in separate mice with a heterozygous knockout of the neurofibromatosis gene Nf1
-
-
Manually annotated by BRENDA team
C57BL/6 mice
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-
Manually annotated by BRENDA team
male corticotropin-releasing hormone knockout mice (C57B1/129SV, 20-25 g, approximately 12 weeks old) and wild type mice
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6
C57BL/6 mice
-
-
Manually annotated by BRENDA team
male Spargue-Dawley rats
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-
Manually annotated by BRENDA team
male Sprague-Dawley rats, 260-320 g, approximately 12 weeks old
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-
Manually annotated by BRENDA team
Wistar rats, 6-12 weeks, either sex. In the immunohistochemistry experiment phenylethanolamine N-methyltransferase demonstrate strong staining in the majority of cells, representing the adrenergic cell population.
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-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-hydroxyphenylethanolamine + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
show the reaction diagram
-
i.e. o-octopamine
-
-
?
3,4-dichlorophenyl ethanolamine + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
3,4-dichlorophenylethanolamine + S-adenosyl-L-methionine
N-methyl-3,4-dichlorophenylethanolamine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
3,4-dichlorophenylethanolamine + S-adenosyl-L-methionine
N-methyl-3,4-dichlorophenylethanolamine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
3,4-dichlorophenylethylenediamine + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
-
3,4-dichlorophenylethylenediamine + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
3,4-dihydroxynorephedrine + S-adenosyl-L-methionine
3,4-dihydroxyephedrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
18% of the activity with normetanephrine
-
-
?
3-chloro-4-hydroxyphenylethanolamine + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
-
3-chloro-4-hydroxyphenylethanolamine + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
3-hydroxyphenylethanolamine + S-adenosyl-L-methionine
N-methyl-m-octopamine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
3-hydroxyphenylethanolamine + S-adenosyl-L-methionine
N-methyl-m-octopamine + S-adenosyl-L-homocysteine
show the reaction diagram
-
i.e. m-octopamine
-
-
?
3-trifluoromethylphenylethanolamine + S-adenosyl-L-methionine
?
show the reaction diagram
P11086
-
-
-
?
4-hydroxynorephedrine + S-adenosyl-L-methionine
4-hydroxyephedrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
18% of the activity with normetanephrine
-
-
?
4-hydroxyphenylethanolamine + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
show the reaction diagram
-
i.e. octopamine
-
-
?
9-methylnorharman + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
show the reaction diagram
-
2N-methylation, PNMT catalyzes the 2N-methylation of beta-carbolines, forming 2N-methylated beta-carbolinium cations, which are structural and functional analogs of the Parkinsonian-inducing toxin MPP+
-
-
?
anti-9-amino-6-(trifluoromethyl)benzonorbornene + S-adenosyl-L-methionine
?
show the reaction diagram
P11086
-
-
-
?
cis-(1R,2S)-2-amino-1-tetralol + S-adenosyl-L-methionine
cis-(1R,2S)-2-methylamino-1-tetralol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
D-norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
D-norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
15% of the activity with normetanephrine
-
-
?
DL-m-hydroxyphenylethanolamine + S-adenosyl-L-methionine
neosynephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
60% of the activity with normetanephrine
-
-
?
DL-neo-synephrine + S-adenosyl-L-methionine
3-hydroxy-alpha-[(dimethylamine)methyl]benzenemethanol + S-adenosyl-L-homocysteine
show the reaction diagram
-
20% of the activity with normetanephrine
-
-
?
DL-octopamine + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
show the reaction diagram
-
18% of the activity with normetanephrine
-
-
?
dopamine + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
epinephrine + S-adenosyl-L-methionine
? + D-adenosylhomocysteine
show the reaction diagram
-
-
-
-
?
L-norephedrine + S-adenosyl-L-methionine
ephedrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
14% of the activity with normetanephrine
-
-
?
L-norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
-
L-norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
L-norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
?
norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
-
norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
?
norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
normetanephrine + S-adenosyl-L-methionine
metanephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
normetanephrine + S-adenosyl-L-methionine
metanephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
normetanephrine + S-adenosyl-L-methionine
metanephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
i.e. 3-methoxy-4-hydroxyphenylethanolamine
-
-
-
octopamine + S-adenosyl-L-methionine
N-methyloctopamine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
phenylethanolamine + S-adenosyl-L-methionine
N-methylphenylethanolamine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
phenylethanolamine + S-adenosyl-L-methionine
N-methylphenylethanolamine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
phenylethanolamine + S-adenosyl-L-methionine
N-methylphenylethanolamine + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
phenylethanolamine + S-adenosyl-L-methionine
N-methylphenylethanolamine + S-adenosyl-L-homocysteine
show the reaction diagram
-
72% of the activity with normetanephrine
-
-
?
S-adenosyl-L-methionine + 4-aminomethyl-1,2,3,4-tetrahydroisoquinoline
S-adenosyl-L-homocysteine + ?
show the reaction diagram
P11086
-
-
-
?
S-adenosyl-L-methionine + noradrenaline
S-adenosyl-L-homocysteine + epinephrine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
show the reaction diagram
-
epinephrine is an important neurotransmitter and hormone, and epinephrine is required for normal blood pressure and cardiac filling responses to stress, but is not required for tachycardia during stress or normal cardiovascular function at rest
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
show the reaction diagram
-
last step in biosynthesis of epinephrine
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
show the reaction diagram
-
terminal step in epinephrine biosynthesis
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
show the reaction diagram
Mus musculus C57BL/6
-
epinephrine is an important neurotransmitter and hormone, and epinephrine is required for normal blood pressure and cardiac filling responses to stress, but is not required for tachycardia during stress or normal cardiovascular function at rest
-
-
?
S-adenosyl-L-methionine + phenylethanolamine
S-adenosyl-L-homocysteine + N-methylphenylethanolamine
show the reaction diagram
P11086
-
-
-
?
S-adenosyl-L-methionine + phenylethanolamine
S-adenosyl-L-homocysteine + N-methylphenylethanolamine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + phenylethanolamine
S-adenosyl-L-homocysteine + N-methylphenylethanolamine
show the reaction diagram
P11086
-
-
-
?
S-adenosyl-L-methionine + phenylethanolamine
S-adenosyl-L-homocysteine + N-methylphenylethanolamine
show the reaction diagram
-
-
-
-
?
L-norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
show the reaction diagram
-
21% of the activity with normetanephrine
-
-
?
additional information
?
-
-
final enzyme in the pathway for epinephrine biosynthesis
-
-
-
additional information
?
-
-
enzyme is involved in biosynthesis of epinephrine
-
-
-
additional information
?
-
-
terminal enzyme in epinephrine biosynthesis
-
-
-
additional information
?
-
-
terminal enzyme in the biosynthetic pathway for epinephrine
-
-
-
additional information
?
-
-
the phenylethanolamine N-methyltransferase GRE plays a necessary, but not sufficient role in the transcriptional aspects to the control mechanism. Analyses implicate the participation of sequences in the distal 5promoter of this gene.
-
-
-
additional information
?
-
-
the enzyme binds to the alpha-adrenoreceptor
-
-
-
additional information
?
-
-
the enzyme is involved in norepinephrine pathways
-
-
-
additional information
?
-
-
enzyme does not react with benzylisoquinolines: tetrahydropapaveroline (THP), 6-O-methyl-THP, 4'-O-methyl-THP and norreticuline
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
show the reaction diagram
-
epinephrine is an important neurotransmitter and hormone, and epinephrine is required for normal blood pressure and cardiac filling responses to stress, but is not required for tachycardia during stress or normal cardiovascular function at rest
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
show the reaction diagram
-
last step in biosynthesis of epinephrine
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
show the reaction diagram
-
terminal step in epinephrine biosynthesis
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
show the reaction diagram
Mus musculus C57BL/6
-
epinephrine is an important neurotransmitter and hormone, and epinephrine is required for normal blood pressure and cardiac filling responses to stress, but is not required for tachycardia during stress or normal cardiovascular function at rest
-
-
?
S-adenosyl-L-methionine + phenylethanolamine
S-adenosyl-L-homocysteine + N-methylphenylethanolamine
show the reaction diagram
-
-
-
-
?
9-methylnorharman + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
show the reaction diagram
-
PNMT catalyzes the 2N-methylation of beta-carbolines, forming 2N-methylated beta-carbolinium cations, which are structural and functional analogs of the Parkinsonian-inducing toxin MPP+
-
-
?
additional information
?
-
-
final enzyme in the pathway for epinephrine biosynthesis
-
-
-
additional information
?
-
-
enzyme is involved in biosynthesis of epinephrine
-
-
-
additional information
?
-
-
terminal enzyme in epinephrine biosynthesis
-
-
-
additional information
?
-
-
terminal enzyme in the biosynthetic pathway for epinephrine
-
-
-
additional information
?
-
-
the phenylethanolamine N-methyltransferase GRE plays a necessary, but not sufficient role in the transcriptional aspects to the control mechanism. Analyses implicate the participation of sequences in the distal 5promoter of this gene.
-
-
-
additional information
?
-
-
the enzyme binds to the alpha-adrenoreceptor
-
-
-
additional information
?
-
-
the enzyme is involved in norepinephrine pathways
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
S-adenosyl-L-methionine
-
-
S-adenosyl-L-methionine
-
-
S-adenosyl-L-methionine
-
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(6R)-6-methyl-2-nitro-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
-
(6R)-6-methyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carbonitrile
-
-
(6S)-6-methyl-2-nitro-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
-
(6S)-6-methyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carbonitrile
-
-
(7-nitro-1,2,3,4-tetrahydroisoquinolin-3-yl)methanol
-
-
(R)-3-methyl-1,2,3,4-tetrahydroisoquinoline
-
-
(R)-7-bromo-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline
-
-
(S)-3-methyl-1,2,3,4-tetrahydroisoquinoline
-
-
1,2,3,4-tetrahydrobenz[h]isoquinoline
-
the inhibitor forms hydrophobic interactions with Val53, Met258, Val272, and Val269 in the PNMT active site, binding site structure, overview
1,2,3,4-tetrahydroisoquinoline
-
a nonselective inhibitor
1,2,3,4-tetrahydroisoquinoline
-
-
1,2,3,4-tetrahydroisoquinoline-7-carboxylic acid
-
-
1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
high selectivity
1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
-
1,4-diaminonaphthalene-2,6-disulfonic acid
-
-
-
1-(2,3-dichlorophenyl)ethanamine
-
-
1-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)ethanone
-
-
1-aminoisoquinoline
-
Kd: 14 microM
-
1-phenylmethanamine
-
-
1-thiophen-2-ylmethanamine
-
-
1-thiophen-3-ylmethanamine
-
-
2,3,4,5-tetrahydro-1H-2-benzazepine
-
-
2,3,4,5-tetrahydro-5H-1,4-benzodiazepine
-
-
2,3,4,5-tetrahydro-5H-1,4-benzothiazepine
-
-
2,3,4,5-tetrahydro-5H-1,4-benzoxazepine
-
-
2,3-dichloro-alpha-methylbenzylamine
P11086
-
2,5-Dimethyl-1-aminobenzimidazole
-
-
2-amino-1-methylbenzimidazole
-
Kd: 4.6 microM
-
2-amino-4(7)-hydroxy-benzimidazole
-
Kd: 20 microM
-
2-amino-5(6)-chloro-7(4)-hydroxy-benzimidazole
-
Kd: 14 microM
-
2-amino-5(6)-chloro-benzimidazole
-
Kd: 1.8 microM
-
2-amino-5(6)-fluoro-benzimidazole
-
Kd: 7.2 microM
-
2-aminobenzimidazole
-
Kd: 6.3 microM
2-Aminotetralin
-
most effective inhibitor
2-bromo-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
-
2-bromo-6-(trifluoromethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
-
2-chlorophenylethanolamine
-
-
2-fluorophenylethanolamine
-
-
2-methyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
-
2-nitro-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
-
2-phenylethanamine
-
-
2-Phenylethylamine
-
-
2-thiophen-2-ylethanamine
-
-
3,4-dichloroamphetamine
-
-
3,4-dichloroamphetamine
P11086
-
3,4-Dichlorophenylethanolamine
-
substrate inhibition
3,4-Dichlorophenylethanolamine
-
-
3,4-dichlorophenylethylenediamine
-
substrate inhibition
3,4-dihydroxyphenylethanolamine
-
-
3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline
-
little selectivity
3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
very high selectivity
3-(fluoromethyl)-7-(thiomorpholin-4-ylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
-
3-(fluoromethyl)-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
high selectivity
3-(fluoromethyl)-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
very high selectivity
3-(fluoromethyl)-N-(3,3,3-trifluoropropyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
-
3-(trifluoromethyl)-1,2,3,4-tetrahydro[1]benzothieno[3,2-c]pyridine
-
-
3-bromophenylethanolamine
-
-
3-butyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
little selectivity
3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
-
3-difluoromethyl-7-(ethylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
-
3-difluoromethyl-7-(N-2,2,2-trifluoroethylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
-
3-difluoromethyl-7-(N-3-methoxypropylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
-
3-difluoromethyl-7-(N-4-nitrophenylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
-
3-difluoromethyl-7-(propylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
-
3-difluoromethyl-7-bromo-1,2,3,4-tetrahydroisoquinoline
-
-
3-difluoromethyl-7-cyano-1,2,3,4-tetrahydroisoquinoline
-
-
3-difluoromethyl-7-iodo-1,2,3,4-tetrahydroisoquinoline
-
-
3-difluoromethyl-7-methylsulfonyl-1,2,3,4-tetrahydroisoquinoline
-
-
3-difluoromethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
-
3-difluoromethyl-7-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
-
3-ethyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
moderate selectivity
3-ethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
moderate selectivity
3-ethyl-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
moderate selectivity
3-fluoromethyl-7-(2,2,2-trifluoroethylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
-
3-fluoromethyl-7-(3,3,3-trifluoropropylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
-
3-fluoromethyl-7-(4,4,4-trifluorobutylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
-
3-fluoromethyl-7-(4-chlorobenzylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
-
3-fluoromethyl-7-(N-benzylaminosulfonyl)-1,2,3,4-tetrahydrosioquinoline
-
-
3-fluoromethyl-7-(N-methylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
-
3-fluoromethyl-7-aminosulfonyl-1,2,3,4-tetrahydroisoquinoline
-
-
3-fluoromethyl-7-azido-1,2,3,4-tetrahydrosioquinoline
-
-
3-fluoromethyl-7-bromo-1,2,3,4-tetrahydroisoquinoline
-
-
3-fluoromethyl-7-cyano-1,2,3,4-tetrahydroisoquinoline
-
-
3-fluoromethyl-7-iodo-1,2,3,4-tetrahydroisoquinoline
-
-
3-fluoromethyl-7-iodo-1,2,3,4-tetrahydroisoquinoline
-
-
3-fluoromethyl-7-isothiocyanato-1,2,3,4-tetrahydroisoquinoline
-
-
3-fluoromethyl-7-methanesulfonyl-1,2,3,4-tetrahydroisoquinoline
-
-
3-fluoromethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
-
3-fluoromethyl-7-propylsulfonyl-1,2,3,4-tetrahydroisoquinoline
-
-
3-fluoromethyl-7-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
-
3-fluoromethyl-7-[N-(4-chlorophenyl)aminosulfonyl]-1,2,3,4-tetrahydroisoquinoline
-
-
3-hydroxyethyl-7-bromo-1,2,3,4-tetrahydroisoquinoline
-
-
3-hydroxyethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
moderate selectivity
3-hydroxyethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
-
3-hydroxymethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
high selectivity
3-hydroxypropyl-7-bromo-1,2,3,4-tetrahydroisoquinoline
-
extension of the 3-hydroxyalkyl chain by just one carbon results in a significant loss in phenylethanolamine N-methyltransferse inhibitory potency
3-hydroxypropyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
moderate selectivity
3-hydroxypropyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
extension of the 3-hydroxyalkyl chain by just one carbon results in a significant loss in phenylethanolamine N-methyltransferse inhibitory potency
3-isopropyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
little selectivity
3-methyl-1,2,3,4-tetrahydroisoquinoline
-
little selectivity
3-methyl-1,2,3,4-tetrahydroisoquinoline
-
-
3-methyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
high selectivity
3-methyl-1,2,3,4-tetrahydro[1]benzothieno[3,2-c]pyridine
-
-
3-methyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
high selectivity
3-methyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
-
3-methyl-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
high selectivity
3-Phenylpropylamine
-
-
3-propyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
high selectivity
3-propyl-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
moderate selectivity
3-thienylmethylamine
-
inhibits the enzyme and is selective toward the alpha2-adrenoceptor
3-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
-
3-trifluoromethyl-1,2,3,4-tetrahydroisoquinolines
-
several 3-trifluoromethyl-1,2,3,4-tetrahydroisoquinolines and some enantiomers of 3-trifuoromethyl-1,2,3,4-tetrahydroisoquinolines. For the phenylethanolamine N-methyltransferase inhibitory potency of different 3-trifuoromethyl-1,2,3,4-tetrahydroisoquinolines, compounds bearing a lipophilic 7-substituent show higher potency than compounds bearing a hydrophilic 7-substituent. Comparison to the inhibitory activity of the entantiomers of the most potent racemates show that the R-enantiomers are approximately 4fold as potent as their corresponding S-enantiomers.
-
3-trifluoromethyl-7-bromo-1,2,3,4-tetrahydroisoquinoline
-
-
3-trifluoromethyl-7-cyano-1,2,3,4-tetrahydroisoquinoline
-
-
3-trifluoromethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
-
4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
-
4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carbonitrile
-
-
4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide
-
-
4-(benzo[d][1,3]dioxol-5-ylamino)-4-oxobutanoic acid
-
-
-
4-bromo-1H-imidazole
-
Kd: 170 microM
-
4-bromophenylethanolamine
-
-
4-fluorophenylethanolamine
-
-
4-hydroxyphenylethanolamine
-
-
4-oxo-1,4-dihydroquinoline-3,7-dicarboxylic acid
-
-
-
4-quinolinol
-
Kd: 690 microM
-
5,6-Dichloro-2-aminotetralin
-
0.00093 mM, 50% inhibition, competitive with norepinephrine as substrate
5-chlorobenzimidazole
-
Kd: 97 microM
-
6-(trifluoromethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
-
6-Aminoquinoline
-
Kd: 380 microM
6-Chloropurine
-
Kd: 140 microM
6-methyl-2-nitro-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
-
6-methyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
-
6-methyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carbonitrile
-
-
7,8-dichloro-1,2,3,4-tetrahydroisoquinoline
-
-
7-(3-methoxypropylsulfonyl)-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-(N-4-chlorophenylaminosulfonyl)-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-(N-butylaminosulfonyl)-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-acetamido-1,2,3,4-tetrahydroisoquinoline
-
-
7-allylsulfonyl-1,2,3,4-tetrahydrosioquinoline
-
-
7-aminocarbonyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-aminomethyl-1,2,3,4-tetrahydroisoquinoline dihydrochloride
-
-
7-aminosulfonyl-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
-
7-aminosulfonyl-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
-
7-aminosulfonyl-1,2,3,4-tetrahydroisoquinoline
-
i.e. SK&F 29661
7-aminosulfonyl-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-benzoyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-benzyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-bromo-1,2,3,4-tetrahydrobenzo[h]isoquinoline
-
7-bromo-1,2,3,4-tetrahydroben[h]isoquinoline is 2fold more potent as an inhibitor of phenylethanolamine N-methyltransferase than 1,2,3,4-tetrahydroben[h]isoquinoline.
7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
-
7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
-
7-bromo-1,2,3,4-tetrahydroisoquinoline
-
moderate selectivity
7-bromo-1,2,3,4-tetrahydroisoquinoline
-
-
7-bromo-3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline
-
high selectivity
7-bromo-3-butyl-1,2,3,4-tetrahydroisoquinoline
-
little selectivity
7-bromo-3-ethyl-1,2,3,4-tetrahydroisoquinoline
-
little selectivity
7-bromo-3-hydroxyethyl-1,2,3,4-tetrahydroisoquinoline
-
little selectivity
7-bromo-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline
-
moderate selectivity
7-bromo-3-hydroxypropyl-1,2,3,4-tetrahydroisoquinoline
-
little selcetivity
7-bromo-3-isopropyl-1,2,3,4-tetrahydroisoquinoline
-
little selectivity
7-bromo-3-methyl-1,2,3,4-tetrahydroisoquinoline
-
moderate selectivity
7-bromo-3-methyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-bromo-3-pentyl-1,2,3,4-tetrahydroisoquinoline
-
little selectivity
7-bromo-3-propyl-1,2,3,4-tetrahydroisoquinoline
-
little selectivity
7-bromo-N-triphenylmethyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-butylsulfonyl-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-cyano-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
-
7-cyano-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
-
7-ethylsulfonyl-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-hydroxy-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
-
7-hydroxy-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
-
7-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline oxalate
-
-
7-iodo-1,2,3,4-tetrahydroisoquinoline
-
-
7-iodo-1,2,3,4-tetrahydroisoquinoline
-
-
7-methoxy-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
-
7-methoxy-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
-
7-methoxycarbonyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-methylsulfinyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-methylsulfonyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-methylsulfonyl-3-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-methylthio-1,2,3,4-tetrahydroisoquinoline
-
-
7-nitro-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
-
7-nitro-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
-
7-nitro-1,2,3,4-tetrahydroisoquinoline
-
little selectivity
7-nitro-1,2,3,4-tetrahydroisoquinoline
-
-
7-nitro-3-pentyl-1,2,3,4-tetrahydroisoquinoline
-
little selectivity
7-nitro-3-propyl-1,2,3,4-tetrahydroisoquinoline
-
moderate selectivity
7-phenylsulfonyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-sulfonamido-1,2,3,4-tetrahydroisoquinoline
-
-
7-trichloromethylsulfonyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-trifluoroacetyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
-
8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine
-
-
adenine
-
Kd: 180 microM
benzylamine
-
-
D-norepinephrine
-
substrate inhibition
dopamine
-
competitive inhibition with respect to phenylethanolamine
epinephrine
-
isoenzyme E2, noncompetitive inhibitor of S-adenosyl-L-methionine
epinephrine
-
-
epinephrine
-
noncompetitive with normetanephrine as substrate
human cerebrospinal fluid
-
-
-
L-norepinephrine
-
substrate inhibition
LY134046
-
selective inhibitor, IC50: 0.0019 mM
LY134046
P11086
2,3,4,5-tetrahydro-1H-2-benzyzepine derivate with two chloro substituents on the aromatic ring. Is able to cross the blood-brain barrier.
N-(4-chlorophenyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
-
N-(4-chlorophenyl)-3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
-
N-(4-chlorophenyl)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
-
norepinephrine
-
at high concentrations
norepinephrine
-
4 distinct substrate inhibition patterns: enzyme form E1 is not subject to substrate inhibition, isoenzyme E-2 is inhibited by S-adenosyl-L-methionine and norepinephrine, isoenzyme E-3 and E-4 are inhibited by norepinephrine only, isoenzyme E5 is inhibited only by S-adenosyl-L-methionine
norepinephrine
-
noncompetitive inhibition with phenylethanolamine as substrate, competitive inhibition with normetanephrine as substrate
Octopamine
-
at high concentrations
p-hydroxymercuribenzoate
-
0.00001 mM, 75% loss of activity
PCMB
-
0.01 mM, complete inhibition
Phenylethanolamine
-
at high concentrations
Phenylethylamine
-
competitive inhibition with respect to phenylethanolamine
R-(+)-7-bromo-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline
-
-
S-adenosyl-L-methionine
-
substrate inhibition
S-adenosyl-L-methionine
-
4 distinct substrate inhibition patterns: enzyme form E1 is not subject to substrate inhibition, isoenzyme E-2 is inhibited by S-adenosyl-L-methionine and norepinephrine, isoenzyme E-3 and E-4 are inhibited by norepinephrine only, isoenzyme E5 is inhibited only by S-adenosyl-L-methionine
S-adenosylhomocysteine
-
-
S-adenosylhomocysteine
-
competitive
sinefungin
-
-
SK&F 29661
-
-
-
SKF 29661
P11086
1,2,3,4-tetrahydroisoquinoline derivate
SKF 64139
P11086
1,2,3,4-tetrahydroisoquinoline derivate with two chloro substituents on the aromatic ring. Is able to cross the blood-brain barrier.
trans-(1S,2S)-2-amino-1-tetralol
-
-
tyramine
-
at high concentrations
methanol
-
at nonsaturating concentrations of phenylethanolamine, methanol inhibits in a competitive fashion. With respect to S-adenosyl-L-methionine inhibition by methanol is noncompetitive
additional information
-
7-substituted-1,2,3,4-tetrahydroisoquinolines are potent inhibitors, unfortunately, most of these compounds also exhibit a strong affinity for the alpha2-adrenoreceptor
-
additional information
-
inhibitor docking studies, molecular modelling; the addition of a 7-substituent (NO2, SO2NH2, OMe, OH, or CN) to 1,2,3,4-tetrahydroben[h]isoquinoline does not lead to an increase in phenylethanolamine N-methyltransferase inhibitory potency.
-
additional information
-
inhibitor docking studies, molecular modelling
-
additional information
-
the rank order of phenylethanolamine N-methyltransferase inhibitory potency for the analysed 3,7-disubstituted-1,2,3,4-tetrahydroisoquinoline is CH2F equal to CHF2 decreases to CF3. The 3-difluoromethyl-7-substituted-1,2,3,4-tetrahydroisoquinolines have the proper balance of steric and pKa properties, they are both potent inhibitors of phenylethanolamine N-methyltransferase and highly selective due to low affinity for the alpha2-adrenoceptor.
-
additional information
-
the series of 3-fluoromethyl-7-sulfonyl-1,2,3,4-tetrahydroisoquinolines is more lipophilic but less potent than the correspnding sulfonamides. The interaction of the human phenylethanolamnie N-methyltransferase main chain carbonyl oxygen of Asn39 with the sulfonamide -NH- is likely responsible for much of the enhanced inhibitory potency of the sulfonamides versus the sulfones.
-
additional information
-
importance of protein flexibility in structure-based inhibitor design
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.676
2-hydroxyphenylethanolamine
-
-
0.0008
3,4-Dichlorophenylethanolamine
-
-
0.00132
3,4-Dichlorophenylethanolamine
-
enzyme form H-2
0.00159
3,4-Dichlorophenylethanolamine
-
enzyme form H-1
0.012
3,4-dichlorophenylethylenediamine
-
enzyme form H-2
0.0131
3,4-dichlorophenylethylenediamine
-
enzyme form H-1
0.013
3,4-dihydroxyphenylethanolamine
-
-
0.0024
3-chloro-4-hydroxyphenylethanolamine
-
-
0.089
3-hydroxyphenylethanolamine
-
-
0.366
3-methoxy-4-hydroxy-phenylethanolamine
-
-
0.00055
3-trifluoromethylphenylethanolamine
P11086
wild type enzyme, assay containing S-adenosyl-L-methionine and 3-trifluoromethylphenylethanolamine
0.055
3-trifluoromethylphenylethanolamine
P11086
mutant D267, assay containing S-adenosyl-L-methionine and 3-trifluoromethylphenylethanolamine
0.047
4-aminomethyl-1,2,3,4-tetrahydroisoquinoline
-
-
0.017
4-hydroxyphenylethanolamine
-
-
0.0015
anti-9-amino-6-(trifluoromethyl)benzonorbornene
P11086
wild type enzyme, assay containing S-adenosyl-L-methionine and anti-9-amino-6-(trifluoromethyl)benzonorbornene
0.025
anti-9-amino-6-(trifluoromethyl)benzonorbornene
P11086
mutant D267A, assay containing S-adenosyl-L-methionine and anti-9-amino-6-(trifluoromethyl)benzonorbornene
0.0053
cis-(1R,2S)-2-amino-1-tetralol
-
wild type enzyme, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.0297
D-norepinephrine
-
enzyme form H-1
0.109
D-norepinephrine
-
enzyme form H-2
0.015
L-norepinephrine
-
-
0.0299
L-norepinephrine
-
enzyme form H-2
0.0428
L-norepinephrine
-
enzyme form H-1
0.101
L-norepinephrine
-
-
0.0184
norepinephrine
-
wild-type enzyme
0.05
normetanephrine
-
-
0.0055
Octopamine
-
wild type enzyme, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.07
Phenylethanolamine
-
-
0.077
Phenylethanolamine
-
-
0.095
Phenylethanolamine
-
purified in the absence of reducing agent, dimer, His-tagged
0.099
Phenylethanolamine
-
wild type enzyme, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.1
Phenylethanolamine
P11086
wild type enzyme, radiochemical assay containing S-adenosyl-L-methionine and phenylethanolamine
0.101
Phenylethanolamine
-
mutant E185Q, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.102
Phenylethanolamine
-
mutant E185A, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.179
Phenylethanolamine
-
mutant E219Q, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.226
Phenylethanolamine
-
enzyme form H-2
0.244
Phenylethanolamine
-
enzyme form H-1
0.32
Phenylethanolamine
-
mutant E185D, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.58
Phenylethanolamine
P11086
mutant E219A, radiochemical assay containing S-adenosyl-L-methionine and phenylethanolamine
1.31
Phenylethanolamine
P11086
mutant K57A, radiochemical assay containing S-adenosyl-L-methionine and phenylethanolamine
1.63
Phenylethanolamine
P11086
mutant V53A, radiochemical assay containing S-adenosyl-L-methionine and phenylethanolamine
1.64
Phenylethanolamine
P11086
mutant D267N, radiochemical assay containing S-adenosyl-L-methionine and phenylethanolamine
1.73
Phenylethanolamine
-
mutant Y35F, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
2.05
Phenylethanolamine
P11086
mutant D267A, radiochemical assay containing S-adenosyl-L-methionine and phenylethanolamine
0.0012
S-adenosyl-L-methionine
P11086
wild type enzyme, assay containing S-adenosyl-L-methionine and 3-trifluoromethylphenylethanolamine
0.0013
S-adenosyl-L-methionine
-
mutant E185Q, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.0017
S-adenosyl-L-methionine
-
mutant E185A, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.002
S-adenosyl-L-methionine
P11086
wild type enzyme, assay containing S-adenosyl-L-methionine and anti-9-amino-6-(trifuoromethyl)benzonorbornene
0.0024
S-adenosyl-L-methionine
P11086
mutant D267, assay containing S-adenosyl-L-methionine and 3-trifluoromethylphenylethanolamine
0.0034
S-adenosyl-L-methionine
-
wild type enzyme, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.0034
S-adenosyl-L-methionine
P11086
wild type enzyme, radiochemical assay containing S-adenosyl-L-methionine and phenylethanolamine
0.0035
S-adenosyl-L-methionine
-
purified in the absence of reducing agent, dimer, His-tagged
0.0051
S-adenosyl-L-methionine
P11086
mutant D267A, assay containing S-adenosyl-L-methionine and anti-9-amino-6-(trifluoromethyl)benzonorbornene
0.00543
S-adenosyl-L-methionine
-
enzyme form H-1
0.0067
S-adenosyl-L-methionine
-
mutant E219Q, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.0071
S-adenosyl-L-methionine
P11086
mutant E219A and mutant D267N, radiochemical assay containing S-adenosyl-L-methionine and phenylethanolamine
0.0081
S-adenosyl-L-methionine
P11086
mutant D267A, radiochemical assay containing S-adenosyl-L-methionine and phenylethanolamine
0.0096
S-adenosyl-L-methionine
P11086
mutant V53A, radiochemical assay containing S-adenosyl-L-methionine and phenylethanolamine
0.0117
S-adenosyl-L-methionine
P11086
mutant K57A, radiochemical assay containing S-adenosyl-L-methionine and phenylethanolamine
0.014
S-adenosyl-L-methionine
-
mutant E185D, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.0149
S-adenosyl-L-methionine
-
enzyme form H-2
0.0194
S-adenosyl-L-methionine
-
wild-type enzyme
0.024
S-adenosyl-L-methionine
-
-
0.045
S-adenosyl-L-methionine
-
mutant Y35F, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.089
m-octopamine
-
-
additional information
additional information
-
Km-value of mutant enzymes
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.001
3-trifluoromethylphenylethanolamine
P11086
mutant D267A
0.0083
3-trifluoromethylphenylethanolamine
P11086
wild type enzyme
0.0043
anti-9-amino-6-(trifluoromethyl)benzonorbornene
P11086
mutant D267A
0.0062
anti-9-amino-6-(trifluoromethyl)benzonorbornene
P11086
wild type enzyme
0.0048
cis-(1R,2S)-2-amino-1-tetralol
-
wild type enzyme, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.02
Octopamine
-
wild type enzyme, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.00017
Phenylethanolamine
-
mutant E185Q, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.0028
Phenylethanolamine
-
mutant E185A, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.0142
Phenylethanolamine
-
mutant E185D, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.0175
Phenylethanolamine
-
mutant Y35F, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.043
Phenylethanolamine
-
wild type enzyme, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.045
Phenylethanolamine
-
purified in the absence of reducing agent, dimer, His-tagged
0.0483
Phenylethanolamine
-
mutant D267A, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C.
0.0017
S-adenosyl-L-methionine
P11086
mutant D267N
0.0052
S-adenosyl-L-methionine
P11086
mutant D267A
0.0218
S-adenosyl-L-methionine
P11086
mutant E219A
0.0473
S-adenosyl-L-methionine
P11086
wild type enzyme
0.0567
S-adenosyl-L-methionine
P11086
mutant V53A
0.0658
S-adenosyl-L-methionine
P11086
mutant K57A
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0096
(6R)-6-methyl-2-nitro-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
R-isomer, pH 8.0, 37C
0.15
(6R)-6-methyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carbonitrile
-
R-isomer, pH 8.0, 37C
0.00031
(6S)-6-methyl-2-nitro-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
S-isomer, pH 8.0, 37C
0.0033
(6S)-6-methyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carbonitrile
-
S-isomer, pH 8.0, 37C
0.000017
(7-nitro-1,2,3,4-tetrahydroisoquinolin-3-yl)methanol
-
pH 8.0, 30C, wild-type enzyme
0.000145
(7-nitro-1,2,3,4-tetrahydroisoquinolin-3-yl)methanol
-
pH 8.0, 30C, mutant G57A
0.0383
(R)-3-methyl-1,2,3,4-tetrahydroisoquinoline
-
-
0.00101
(S)-3-methyl-1,2,3,4-tetrahydroisoquinoline
-
-
0.00049
1,2,3,4-tetrahydrobenz[h]isoquinoline
-
pH 8.0, 37C
0.00049
1,2,3,4-tetrahydrobenz[h]isoquinoline
-
pH 7.7, 25C
0.0058
1,2,3,4-tetrahydroisoquinoline
-
pH 7.7, 25C
0.0058
1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.47
1,2,3,4-tetrahydroisoquinoline-7-carboxylic acid
-
-
0.00012
1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 30C, wild-type enzyme
0.00028
1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 37C
0.0069
1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 30C, mutant G57A
0.00009
1-(2,3-dichlorophenyl)ethanamine
-
pH 8.0
0.061
1-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)ethanone
-
pH 8.0, 37C
0.45
1-thiophen-2-ylmethanamine
-
pH 8.0, 37C
0.11
1-thiophen-3-ylmethanamine
-
pH 8.0, 37C
0.00334
2,3,4,5-tetrahydro-1H-2-benzazepine
-
-
0.028
2,3,4,5-tetrahydro-5H-1,4-benzodiazepine
-
-
0.0041
2,3,4,5-tetrahydro-5H-1,4-benzothiazepine
-
-
0.0212
2,3,4,5-tetrahydro-5H-1,4-benzoxazepine
-
-
0.000072
2,3-dichloro-alpha-methylbenzylamine
P11086
binding of the inhibitor to the wild type human phenylethanolamine N-methyltransferase S-adenosyl-L-methionine complex
0.000121
2,3-dichloro-alpha-methylbenzylamine
P11086
wild type enzyme, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.00133
2,3-dichloro-alpha-methylbenzylamine
P11086
free wild type human phenylethanolamine N-methyltransferase
0.0012
2-bromo-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
pH 8.0, 37C
0.00073
2-bromo-6-(trifluoromethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
pH 8.0, 37C
0.021
2-bromo-6-(trifluoromethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
pH 8.0, 37C
0.025
2-methyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
pH 8.0, 37C
0.0026
2-nitro-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
pH 8.0, 37C
0.22
2-Phenylethylamine
-
pH 8.0, 37C
0.3
2-thiophen-2-ylethanamine
-
pH 8.0, 37C
0.00227
3,4-dichloroamphetamine
P11086
binding of the inhibitor to the wild type human phenylethanolamine N-methyltransferase S-adenosyl-L-methionine complex
0.00364
3,4-dichloroamphetamine
P11086
wild type enzyme, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.0148
3,4-dichloroamphetamine
P11086
free wild type human phenylethanolamine N-methyltransferase
0.508
3,4-Dichlorophenylethanolamine
-
enzyme form H-2, substrate inhibition
0.909
3,4-Dichlorophenylethanolamine
-
enzyme form H-1, substrate inhibition
1.138
3,4-dichlorophenylethylenediamine
-
enzyme form H-2, substrate inhibition
1.522
3,4-dichlorophenylethylenediamine
-
enzyme form H-1, substrate inhibition
0.00082
3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.00015
3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 37C
0.0000018
3-(fluoromethyl)-7-(thiomorpholin-4-ylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 30C, mutant G57A
0.000315
3-(fluoromethyl)-7-(thiomorpholin-4-ylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 30C, wild-type enzyme
0.00015
3-(fluoromethyl)-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.00013
3-(fluoromethyl)-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 37C
0.000017
3-(fluoromethyl)-N-(3,3,3-trifluoropropyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 30C, mutant G57A
0.000035
3-(fluoromethyl)-N-(3,3,3-trifluoropropyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 30C, wild-type enzyme
0.017
3-(trifluoromethyl)-1,2,3,4-tetrahydro[1]benzothieno[3,2-c]pyridine
-
pH 8.0, 37C
0.0066
3-butyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.0034
3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor
0.0032
3-difluoromethyl-7-(ethylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor
0.00025
3-difluoromethyl-7-(N-2,2,2-trifluoroethylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor
0.0053
3-difluoromethyl-7-(N-3-methoxypropylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor
0.037
3-difluoromethyl-7-(N-4-nitrophenylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor
0.0021
3-difluoromethyl-7-(propylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor
0.000094
3-difluoromethyl-7-bromo-1,2,3,4-tetrahydroisoquinoline
-
radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor
0.0031
3-difluoromethyl-7-cyano-1,2,3,4-tetrahydroisoquinoline
-
radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor
0.0002
3-difluoromethyl-7-iodo-1,2,3,4-tetrahydroisoquinoline
-
radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor
0.006
3-difluoromethyl-7-methylsulfonyl-1,2,3,4-tetrahydroisoquinoline
-
radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor
0.00017
3-difluoromethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor
0.000067
3-difluoromethyl-7-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor
0.0018
3-ethyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 37C
0.00049
3-ethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.00051
3-ethyl-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 37C
0.0014
3-fluoromethyl-7-(2,2,2-trifluoroethylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate and three concentrations of inhibitor with a radiochemical assay.
0.0013
3-fluoromethyl-7-(3,3,3-trifluoropropylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate and three concentrations of inhibitor with a radiochemical assay.
0.067
3-fluoromethyl-7-(4,4,4-trifluorobutylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate and three concentrations of inhibitor with a radiochemical assay.
0.032
3-fluoromethyl-7-(4-chlorobenzylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate and three concentrations of inhibitor with a radiochemical assay.
0.0065
3-fluoromethyl-7-(N-benzylaminosulfonyl)-1,2,3,4-tetrahydrosioquinoline
-
-
0.0024
3-fluoromethyl-7-(N-methylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
-
0.00066
3-fluoromethyl-7-aminosulfonyl-1,2,3,4-tetrahydroisoquinoline
-
-
0.0017
3-fluoromethyl-7-azido-1,2,3,4-tetrahydrosioquinoline
-
-
0.00064
3-fluoromethyl-7-bromo-1,2,3,4-tetrahydroisoquinoline
-
-
0.0011
3-fluoromethyl-7-cyano-1,2,3,4-tetrahydroisoquinoline
-
-
0.000073
3-fluoromethyl-7-iodo-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0
0.00021
3-fluoromethyl-7-iodo-1,2,3,4-tetrahydroisoquinoline
-
-
0.00057
3-fluoromethyl-7-isothiocyanato-1,2,3,4-tetrahydroisoquinoline
-
-
0.0016
3-fluoromethyl-7-methanesulfonyl-1,2,3,4-tetrahydroisoquinoline
-
-
0.54
3-fluoromethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
-
0.0024
3-fluoromethyl-7-propylsulfonyl-1,2,3,4-tetrahydroisoquinoline
-
inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate and three concentrations of inhibitor with a radiochemical assay.
0.00032
3-fluoromethyl-7-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
-
0.00074
3-fluoromethyl-7-[N-(4-chlorophenyl)aminosulfonyl]-1,2,3,4-tetrahydroisoquinoline
-
-
0.00035
3-hydroxyethyl-7-bromo-1,2,3,4-tetrahydroisoquinoline
-
-
0.00051
3-hydroxyethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0
0.00051
3-hydroxyethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
-
0.000047
3-hydroxymethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0
0.0017
3-hydroxypropyl-7-bromo-1,2,3,4-tetrahydroisoquinoline
-
-
0.0014
3-hydroxypropyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0
0.0014
3-hydroxypropyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
-
0.0046
3-isopropyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.0014
3-methyl-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.000077
3-methyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 37C
0.000067
3-methyl-1,2,3,4-tetrahydro[1]benzothieno[3,2-c]pyridine
-
pH 8.0, 37C
0.000072
3-methyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.000034
3-methyl-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 37C
0.00012
3-propyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 37C
0.00092
3-propyl-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 37C
0.015
3-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
-
0.00052
3-trifluoromethyl-7-bromo-1,2,3,4-tetrahydroisoquinoline
-
-
0.013
3-trifluoromethyl-7-cyano-1,2,3,4-tetrahydroisoquinoline
-
-
0.002
3-trifluoromethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
-
0.037
4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
pH 8.0, 37C
0.015
4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carbonitrile
-
pH 8.0, 37C
0.1
4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide
-
pH 8.0, 37C
0.00027
5,6-Dichloro-2-aminotetralin
-
-
0.04
6-(trifluoromethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
pH 8.0, 37C
0.0058
6-methyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
-
pH 8.0, 37C
0.0000031
7,8-dichloro-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0
0.0000031
7,8-dichloro-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.072
7-(3-methoxypropylsulfonyl)-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
inhibition constants are determined using four concentrations of phenylethanolamnie as the variable substrate and three concentrations of inhibitor with a radiochemical assay.
0.0009
7-(N-4-chlorophenylaminosulfonyl)-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor
0.0056
7-(N-butylaminosulfonyl)-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor
0.19
7-acetamido-1,2,3,4-tetrahydroisoquinoline
-
-
0.0098
7-allylsulfonyl-1,2,3,4-tetrahydrosioquinoline
-
-
0.064
7-aminocarbonyl-1,2,3,4-tetrahydroisoquinoline
-
-
1.9
7-aminomethyl-1,2,3,4-tetrahydroisoquinoline dihydrochloride
-
-
0.033
7-aminosulfonyl-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
-
0.00068
7-aminosulfonyl-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor
0.0029
7-benzoyl-1,2,3,4-tetrahydroisoquinoline
-
-
0.061
7-benzyl-1,2,3,4-tetrahydroisoquinoline
-
-
0.00022
7-bromo-1,2,3,4-tetrahydrobenzo[h]isoquinoline
-
-
0.00022
7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
pH 8.0, 37C
0.00022
7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
pH 7.7, 25C
0.000056
7-bromo-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.000023
7-bromo-3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.0076
7-bromo-3-butyl-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.00048
7-bromo-3-ethyl-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.00035
7-bromo-3-hydroxyethyl-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0
0.000012
7-bromo-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0
0.0017
7-bromo-3-hydroxypropyl-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0
0.0044
7-bromo-3-isopropyl-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.000017
7-bromo-3-methyl-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.011
7-bromo-3-pentyl-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.00048
7-bromo-3-propyl-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.00029
7-bromo-N-triphenylmethyl-1,2,3,4-tetrahydroisoquinoline
-
-
0.018
7-butylsulfonyl-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate and three concentrations of inhibitor with a radiochemical assay.
0.0023
7-cyano-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
-
0.014
7-ethylsulfonyl-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
inhibition constants are determine using four concentrations of phenylethanolamnie as the variable substrate and three concentrations of inhibitor with a radiochemical assay.
0.00091
7-hydroxy-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
-
0.011
7-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline oxalate
-
-
0.00004
7-iodo-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 30C, wild-type enzyme
0.00037
7-iodo-1,2,3,4-tetrahydroisoquinoline
-
-
0.00037
7-iodo-1,2,3,4-tetrahydroisoquinoline
-
-
0.00074
7-iodo-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 30C, mutant G57A
0.0021
7-methoxy-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
-
0.0067
7-methoxycarbonyl-1,2,3,4-tetrahydroisoquinoline
-
-
0.045
7-methylsulfinyl-1,2,3,4-tetrahydroisoquinoline
-
-
0.0013
7-methylsulfonyl-1,2,3,4-tetrahydroisoquinoline
-
-
0.036
7-methylsulfonyl-3-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
-
0.00061
7-methylthio-1,2,3,4-tetrahydroisoquinoline
-
-
0.0009
7-nitro-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
-
0.00004
7-nitro-1,2,3,4-tetrahydroisoquinoline
P11086
wild type enzyme, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.000056
7-nitro-1,2,3,4-tetrahydroisoquinoline
P11086
binding of the inhibitor to the wild type human phenylethanolamine N-methyltransferase S-adenosyl-L-methionine complex
0.00007
7-nitro-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 30C, wild-type enzyme
0.000078
7-nitro-1,2,3,4-tetrahydroisoquinoline
P11086
wild type enzyme, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.00012
7-nitro-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.00013
7-nitro-1,2,3,4-tetrahydroisoquinoline
P11086
mutant V53A, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.00074
7-nitro-1,2,3,4-tetrahydroisoquinoline
P11086
mutant K57A, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.00137
7-nitro-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 30C, mutant G57A
0.00236
7-nitro-1,2,3,4-tetrahydroisoquinoline
P11086
free wild type human phenylethanolamine N-methyltransferase
0.0179
7-nitro-1,2,3,4-tetrahydroisoquinoline
P11086
mutant E219A, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.067
7-nitro-1,2,3,4-tetrahydroisoquinoline
P11086
mutant D267A, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.0098
7-nitro-3-pentyl-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.00053
7-nitro-3-propyl-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0, 37C
0.014
7-phenylsulfonyl-1,2,3,4-tetrahydroisoquinoline
-
-
0.00028
7-sulfonamido-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0
0.00056
7-sulfonamido-1,2,3,4-tetrahydroisoquinoline
-
-
0.0013
7-trichloromethylsulfonyl-1,2,3,4-tetrahydroisoquinoline
-
-
0.0057
7-trifluoroacetyl-1,2,3,4-tetrahydroisoquinoline
-
-
0.00018
7-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
-
0.000012
8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine
-
pH 8.0
0.00026
8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine
-
-
0.17
benzylamine
-
pH 8.0, 37C
0.109
D-norepinephrine
-
enzyme form H-2, substrate inhibition
8.298
D-norepinephrine
-
enzyme form H-1, substrate inhibition
8
dopamine
-
competitive with phenylethanolamine
0.054
epinephrine
-
-
0.165
L-norepinephrine
-
enzyme form H-1, substrate inhibition
0.631
L-norepinephrine
-
enzyme form H-2, substrate inhibition
0.0000044
LY134046
P11086
wild type enzyme, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.0000225
LY134046
P11086
mutant V53A, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.0000906
LY134046
P11086
mutant K57A, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.00059
LY134046
P11086
mutant D267A, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.0000013
N-(4-chlorophenyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 30C, mutant G57A
0.00021
N-(4-chlorophenyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 30C, wild-type enzyme
0.000001
N-(4-chlorophenyl)-3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 30C, mutant G57A
0.000046
N-(4-chlorophenyl)-3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 30C, wild-type enzyme
0.00027
N-(4-chlorophenyl)-3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0
0.0000014
N-(4-chlorophenyl)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 30C, mutant G57A
0.000039
N-(4-chlorophenyl)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
pH 8.0, 30C, wild-type enzyme
0.0059
norepinephrine
-
noncompetitive with phenylethanolamine
3.6
Phenylethylamine
-
competitive with phenylethanolamine
0.0000049
R-(+)-7-bromo-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline
-
pH 8.0
0.0124
S-adenosyl-L-methionine
-
enzyme form H-2, substrate inhibition
0.0894
S-adenosyl-L-methionine
-
enzyme form H-1, substrate inhibition
0.000057
SKF 29661
P11086
binding of the inhibitor to the wild type human phenylethanolamine N-methyltransferase S-adenosyl-L-methionine complex
0.00012
SKF 29661
P11086
wild type enzyme, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.00062
SKF 29661
P11086
mutant V53A, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.00284
SKF 29661
P11086
free wild type human phenylethanolamine N-methyltransferase
0.0069
SKF 29661
P11086
mutant D57A, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.189
SKF 29661
P11086
mutant E219A, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.321
SKF 29661
P11086
mutant D267A, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.00000155
SKF 64139
P11086
wild type enzyme, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.000019
SKF 64139
P11086
mutant V53A, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.0000265
SKF 64139
P11086
mutant K57A, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.000999
SKF 64139
P11086
mutant D267A, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.001375
SKF 64139
P11086
mutant E219A, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
0.0021
trans-(1S,2S)-2-amino-1-tetralol
-
wild type enzyme, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30C. The concentration of S-adenosyl-L-methionine is fixed on 5 microM.
0.00312
LY134046
P11086
mutant E219A, inhibition assay containing a fixed concentration of S-adenosyl-L-methionine and variable concentrations of the inhibitor and phenylethanolamine
additional information
additional information
-
-
-
additional information
additional information
-
enzyme kinetics using competitive tight-binding inhibition routine
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0019
LY134046
-
selective inhibitor, IC50: 0.0019 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0000137
-
pH 8.5, 37C
0.00658
-
-
9.42
-
enzyme form E-5 from young rabbit
11.5
-
enzyme form E-5 from adult
35.9
-
enzyme form E-1 from young rabbit
51.6
-
enzyme form E-1 from adult
53.5
-
enzyme form E-4 from young rabbit
89.4
-
enzyme form E-4 from adult
175
-
enzyme form E-3 from young rabbit
188
-
enzyme form E-2 from adult
additional information
-
-
additional information
-
-
additional information
-
activity tissue distribution, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5 - 8.2
-
phosphate buffer
7.7
-
assay at, docking to alpha-adenosyl receptor
7.9
-
Tris or borate buffer
8 - 9
-
Tris buffer
8
-
assay at, docking to inhibitors
8
-
assay at
8.5
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
assay at, docking to alpha-adenosyl receptor
25
-
assay at
30
-
assay at
37
-
assay at, docking to inhibitors
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
pheochromocytoma cell line
Manually annotated by BRENDA team
-
pheochromocytoma cell line
Manually annotated by BRENDA team
-
adrenal medulla has considerably more activity than the cortex
Manually annotated by BRENDA team
-
adrenergic chromaffin cells and medullary tissue
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
-
phenylethanolamine N-methyltransferase mRNA levels are 30fold increased by dexamethasone. Glial cell line-derived neurotrophic factor and cpt-cAMP each exert negligible influence on baseline phenylethanolamine N-methyltransferase mRNA levels. cAMP effectively blocks dexamethasone induction of phenylethanolamine N-methyltransferase mRNA.
Manually annotated by BRENDA team
-
transient developmental burst in enzyme expression in the embryonic rat heart from E9.5 to E13.0
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
neuroendocrine tumour of chromaffin cells
Manually annotated by BRENDA team
-
pheochromocytomas are tumors of adrenal chromaffin cells. Phenylethanolamine N-methyltransferase mRNA levels are markedly increased by glucocorticoid administration. Dexamethasone elicites approximately 800fold increases in phenylethanolamine N-methyltransferase mRNA levels in mouse pheochromocytoma 862L cells and approximately 75fold increases for mouse pheochromocytoma 10/9CR1 cells. Glial cell line-derived neurotrophic factor and cpt-cAMP alone each produce little or no change in baseline phenylethanolamine N-methyltransferase mRNA levels. In both cell lines, dexamethasone-stimulated increases in phenylethanolamine N-methyltranferase mRNA levels are reduced approximately 90% by prior tratment with cAMP. Glial cell line-derived neurotrophic factor reduces dexamethasone effects on phenylethanolamine N-methyltransferase mRNA levels by 40% in mouse pheochromocytoma 862L cells, while not supressing the dexamethasone response in mouse pheochromocytoma 10/9CRC1 cells. Pretreatment with cAMP and afterwards treatment with glial cell line-derived neurotrophic factor before additon of dexamethasone reduced phenylethanolamine N-methyltransferase expression in mouse pheochromocytoma 862L and 10/9CRC1 cells to 0.1% and 5.5% of their corresponding DEX induced maxima.
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
-
higher levels of phenylethanolamine N-methyltransferase in stellate ganglia of mice compared with rats. Phenylethanolamine N-methyltransferase mRNA is present in stellate ganglia. Immobilization stress increases the gene expression of phenylethanolamine N-methyltransferase in stellate ganglia of rats, the highest levels of phenylethanolamine N-methyltransferase mRNA are immediatetly after and 3 h after the end of a stressful stimulus, while recovery to control levels occurs 6 h after the termination of immobilization. Immobilization repeated seven times further increases mRNA levels of phenylethanolamine N-methyltransferase in stellate ganglia of rats. There is no change in phenylethanol N-methyltransferase protein levels in stellate ganglia after a single immobilization, but protein levels are increased after repeated immobilization stress exposure.
Manually annotated by BRENDA team
-
higher levels of phenylethanolamine N-methyltransferase in stellate ganglia of mice compared with rats. There are differences in noradrenaline and adrenaline concentration in stellate ganglia between wild type and knock out mice under basal and under stress conditons. Phenylethanolamine N-methyltransferase mRNA is present in stellate ganglia. There is an increase in phenylethanolamine N-methyltransferase mRNA levels in stellate ganglia of WT mice after exposure to single and also an increase in phenylethanolamine N-methyltransferase mRNA and protein levels after repeated immobilization compared with the unstressed control group. In corticotropin-releasing hormone knockout mice, no increase in phenylethanolamine N-methyltransferase gene expression and protein level occurs either after single or after repeated immobilization stress exposure.
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
additional information
P40935
barely detectable in the spleen
Manually annotated by BRENDA team
additional information
-
PNMT activity is low in the resting phase and increases to the peak in the prespawning and spawning phases. Maintenance of the fish under long photoperiods and high temperature stimulates activity
Manually annotated by BRENDA team
additional information
-
activity tissue distribution, overview
Manually annotated by BRENDA team
additional information
Mus musculus C57BL/6
-
activity tissue distribution, overview
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Mus musculus C57BL/6
-
-
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30000
-
SDS-PAGE
672345
30280
-
analytical ultracentrifugation, non tagged phenylethanolamine N-methyltransferase, monomer
672345
34000
-
gel filtration
639438
37000
-
gel filtration
639432
38000
-
sucrose density gradient centrifugation
639431
60550
-
analytical ultracentrifugation, non tagged phenylethanolamine N-methyltransferase, dimer
672345
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
gel filtration reveals the presence of two species at elution volumes consistent with monomeric and dimeric human phenylethanolamine N-methyltransferase. The more prominent peak corresponds to the dimer form. The amount of dimer can be reduced either by using a more elute concentration of the protein or by the addition of 0.5 mM DTT to the running buffer. SDS-PAGE can not distinguish between the two forms. Native PAGE clearly distinguishes between the two forms of human phenylethanolamine N-methyltransferase. Crystals from the dimer fraction grow faster. Monomer and dimer human phenylethanolamine N-methyltransferase have similar kinetic constatns. The monomer-dimer equilibruim in analytical ultracentrifugation for the dimer frations of phenylethanolamine N-methyltransferase-His and C48A phenylethanolamine N-methyltransferase is 10fold lower than for the monomer fractions (Kd 35-64 microM and 305-551 microM, respectively).
monomer
-
1 * 35000, enzyme form E-3, SDS-PAGE, 1 * 40000, enzyme form E-1, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
no glycoprotein
-
enzyme contains no carbohydrate
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystallized in complex with an inhibitor and the cofactor product S-adenosyl-L-homocysteine using hanging-drop technique with PEG 6000 and lithium chloride as precipitant
-
hanging drop vapor diffusion using drops of 1 microl of protein and 1 microl of precipitant over 100 microl of precipitant [ 5-8% PEG 6K, 0.25 M LiCl, and 0.1 M sodium cacodylate (pH 5.5-6.0)]
-
hanging drop vapour diffusion method is used with 2 mircol drops on 3 M sealed over 500 mircol or 100 microl precipitant in 24-well or 96-well trays. In the absence of reducing agents crystals grow on protein concentrations of 30 to 40 mg/ml and appear in two or three days. The addition of DTT inhibits formation of crystals under the same condition. Reduced and oxidized glutathione are added to PEG/LiCl crystallisation conditions, crystals only grow in drops where the amount of oxidized glutathione is higher than reduced, the ratio of 1:20 (reduced glutathione/oxidized glutathione) gives the largest crystals.
-
hanging drop vapour diffusion on 3 M tape with 1 microl protein/ligand mixture plus 1 microl precipitant over 100 microl precipitant (0.6-0.8 M NH4H2PO4, 0.1 M citrate pH 5.3-5.8). The human phenylethanolamine N-methyltransferase S-adenosyl-L-homocysteine SKF 64139 structure is solved by difference Fourier methods and refines at 2.4 A resolution. A hydrophilic inhibitor does not bind in a distinclty differnt orientation than a hydrophobic inhibitor.
P11086
in complex with inhibitors 3-hydroxymethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline, 7-bromo-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline, 3-hydroxyethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline, 3-hydroxypropyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
-
in complex with S-adenosyl-L-homocysteien and either 7-iodo-1,2,3,4-tetrahydroisoquinoline or 8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine or 7-sulfonamido-1,2,3,4-tetrahydroisoquinoline
-
model is prepared on the basis of X-ray crystal structure of hPNMT in complex with S-adenosyl-L-homocysteine (AdoHcy) and the inhibitor SK&F 29661
-
purified recombinant His6-tagged wild-type and mutant K75A enzymes in complex with S-adenosyl-L-methionine or S-adenosyl-L-homocysteine, and with inhibitors (R)-4, (R)-5, (R)-6, and (R)-7, X-ray diffraction structure determination and analysis at 2.0-2.8 A resolution
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
39
-
stable for at least 50 min
639431
45
-
activity is rapidly destroyed
639431
60
-
5 min, littel activity remains
639433
additional information
-
presence of 2.5 mM normetanephrine has no effect on the heat denaturation, 1 mM S-adenosyl-L-methionine decreases the rate of inactivation
639431
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-10C, stable for at least 1 month
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
at least 4 active charged isoenzymes
-
6X-histidine tagged phenylethanolamine N-methyltransferase purified on a 10 ml column and with gel filtration. Non-tagged phenylethanolamine N-methyltransferase is purified with DEAE-Sepharose and gel filtration.
-
His-Select HC nickel affninity column and gel filtration
P11086
recombinant C-terminally His6-tagged wild-type and mutant enzymes
-
using Ni-NTA chromatography
-
5 charge isoenzymes: E-1, E-2, E-3, E-4, E-5
-
enzyme form H-1 and H-2
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in a mouse C127 cell line
-
C-terminally His-tagged hPNMT is expressed in Escherichia coli
-
expressed in Escherichia coli
-
expressed in Escherichia coli as a His-tagged fusion protein
-
expressed in Escherichia coli strain BL21(DE3)-pLysS
P11086
expressed in Escherichia coli strain BL21(DE3)pLysS
-
expressed in Eschrischia coli; expression of C-terminally His6-tagged wild-type enzyme
-
expression of C-terminally His6-tagged wild-type and mutant enzymes
-
expression of wild-type enzyme and mutant enzymes in Escherichia coli
-
gene PNMT, genotyping of rs3764351 and rs876493 polymorphisms haplotypes in Japanese women, overview
-
human phenylethynolamine N-methyltransferase with a C-terminal hexahistidine tag is expressed in Escherichia coli
-
expression analysis, transcriptional response of the PNMT gene to GDNF and cpt-cAMP involves distal portions of the PNMT promoter, transient expression of PNMT promoter constructs in MPC 10/9CRC1 cultures
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C131S
-
mutant enzyme shows similar KM-values and maximal velocity to those of the wild-type enzyme
C139A
-
the C139A mutant separates into two forms on gel filtration, consistent with a monomer and dimer form, the equilibrium is significantly shifted in favour of the monomer. C139A mutant has similar kinetic constants as the wild type human phenylethanolamine N-methyltransferase
C139S
-
mutant enzyme shows similar KM-values and maximal velocity to those of the wild-type enzyme
C183S
-
mutant enzyme shows markedly reduced enzyme activity with less than 3% of the maximal activity of the wild-type enzyme, and ca. sixfold increased apparent KM-value for both substrates
C48A
-
the C48A mutant separates into two forms on gel filtration, consistent with a monomer and dimer form, the equilibrium is significantly shifted in favour of the monomer. C48A mutant has similar kinetic constants as the wild type human phenylethanolamine N-methyltransferase. The monomer-dimer equilibrium in analytical ultracentrifugation for the dimer fractions of phenylethanolamine N-methyltransferase-His and C48A phenylethanolamine N-methyltransferase is 10fold lower than for the monomer fractions (Kd 35-64 microM and 305-551 microM, respectively). The relative Kd values show that C48A phenylethanolamine N-methyltransferase is less likely to form dimer than phenylethanolamine N-methyltransferase-His.
C48A/C139A
-
similar kinetic constants as the wild type human phenylethanolamine N-methyltransferase
C48S
-
mutant enzyme shows similar KM-values and maximal velocity to those of the wild-type enzyme
C60S
-
mutant enzyme shows similar KM-values and maximal velocity to those of the wild-type enzyme
C91S
-
mutant enzyme shows similar KM-values and maximal velocity to those of the wild-type enzyme
D267A
P11086
higher Km and lower kcat values than wild type enzyme
E185A
-
Kcat value is reduced by 15fold. Similar Km for phenylethanolamine and slightly lower Km for AdoMet than the wild type enzyme.
E185D
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Kcat value is reduced by 3fold. Moderately increased Km values for phenylethanolamine and AdoMet
E185Q
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kcat value reduced by about 300fold. Similar Km for phenylethanolamine and slightly lower Km for AdoMet than the wild type enzyme.
E185Q
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mutant has the same Km value as the wild-type hPNMT but extremely lower kcat value. E185Q mutation presents obvious structural changes in the active site
E219A
P11086
higher Km and lower kcat values than wild type enzyme
E219Q
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The E219Q mutant has no effect on the catatlytic rate.
E219Q
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mutation has little effect on the kcat value. The bridge water still forms two hydrogen bonds between Gln219 and Glu185
K57A
P11086
higher Km and higher kcat values than wild type enzyme
V53A
P11086
higher Km and higher kcat values than wild type enzyme
K75A
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crystal structure determination and comparison to the wild-type enzyme structure
additional information
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rs3764351 and rs876493 polymorphisms in gene PNMT are correlated to reward dependence, overview
Y35F
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reduced level of binding of phenylethanolamine and AdoMet. The catalytic rate is not greatly affected by the Y35F mutation.
additional information
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construction of enzyme knockout mutant mice, that show resting cardiovascular function, including blood pressure, heart rate, and cardiac output similar to that in wild-type mice, and the basal norepinephrine plasma level is unaltered. However, inhibition of sympathetic innervation with the ganglion blocker hexamethonium causes a 54% smaller decrease in blood pressure in KO mice compared to wild-type mice, and treadmill exercise causes an 11% higher increase in blood pressure, both suggesting impaired vasodilation in KO mice, the enzyme knockout does not change the heart rate response to ganglionic blockade and exercise. KO mice have an increased ratio of left ventricular posterior wall thickness to internal dimensions but do not have cardiac hypertrophy, in restrained, awake KO mice, heart rate and ejection fraction remain unaltered, but cardiac output is significantly reduced because of diminished end-diastolic volume, phenotype, overview
additional information
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construction of PNMT promoter constructs using nested deletion constructs treated with DEX or sequentially with GDNF/cAMP/DEX, the suppression of PNMT induction is reversible
additional information
Mus musculus C57BL/6
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construction of enzyme knockout mutant mice, that show resting cardiovascular function, including blood pressure, heart rate, and cardiac output similar to that in wild-type mice, and the basal norepinephrine plasma level is unaltered. However, inhibition of sympathetic innervation with the ganglion blocker hexamethonium causes a 54% smaller decrease in blood pressure in KO mice compared to wild-type mice, and treadmill exercise causes an 11% higher increase in blood pressure, both suggesting impaired vasodilation in KO mice, the enzyme knockout does not change the heart rate response to ganglionic blockade and exercise. KO mice have an increased ratio of left ventricular posterior wall thickness to internal dimensions but do not have cardiac hypertrophy, in restrained, awake KO mice, heart rate and ejection fraction remain unaltered, but cardiac output is significantly reduced because of diminished end-diastolic volume, phenotype, overview
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
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enzyme serves as a marker for tissues and cells producing epinephrine
additional information
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a potent inhibitor of phenylethanolamine N-methyltransferase, which exhibits a minimal affinity for the alpha-adrenoceptor, would be a useful pharmacological tool for clearly defining the connection between central epinephrine concentrations and blood pressure.
additional information
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a potent inhibitor of phenylethanolamine N-methyltransferase, which exhibits minimal affinity for the alpha2-adrenoceptor and is able to cross the brain-blood-barrier, would be a useful pharmacological tool for defining the role of epinephrine in the central nervous systhem.
additional information
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selective inhibitors of phenylethanolamine N-methyltransferase would be useful pharmacological tools for clearly defining the connection between central epinephrine concentrations and peripheral blood pressure