Information on EC 2.5.1.49 - O-acetylhomoserine aminocarboxypropyltransferase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
2.5.1.49
-
RECOMMENDED NAME
GeneOntology No.
O-acetylhomoserine aminocarboxypropyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
O-acetyl-L-homoserine + methanethiol = L-methionine + acetate
show the reaction diagram
Also reacts with other thiols and H2S, producing homocysteine or thioethers. The name methionine synthase is more commonly applied to EC 2.1.1.13 5-methyltetrahydrofolate-homocysteine S-methyltransferase. The enzyme from baker's yeast also catalyses the reaction of EC 2.5.1.47 cysteine synthase, but more slowly
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
elimination
gamma-replacement
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Cysteine and methionine metabolism
-
-
L-homocysteine biosynthesis
-
-
Metabolic pathways
-
-
S-methyl-5-thio-alpha-D-ribose 1-phosphate degradation II
-
-
cysteine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
O-acetyl-L-homoserine:methanethiol 3-amino-3-carboxypropyltransferase
Also reacts with other thiols and H2S, producing homocysteine or thioethers. The name methionine synthase is more commonly applied to EC 2.1.1.13, methionine synthase. The enzyme from baker's yeast also catalyses the reaction of EC 2.5.1.47 cysteine synthase, but more slowly.
CAS REGISTRY NUMBER
COMMENTARY hide
37290-90-7
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain sG8, pabaA2, YA1
-
-
Manually annotated by BRENDA team
strain sG8, pabaA2, YA1
-
-
Manually annotated by BRENDA team
cattle, Holstein steer
-
-
Manually annotated by BRENDA team
No. 2247, ATCC 14067
-
-
Manually annotated by BRENDA team
Corynebacterium acetophilum
strain A51
-
-
Manually annotated by BRENDA team
Corynebacterium acetophilum A51
strain A51
-
-
Manually annotated by BRENDA team
strain CN3, isolated from a hot spring in Japan
-
-
Manually annotated by BRENDA team
strain CN3, isolated from a hot spring in Japan
-
-
Manually annotated by BRENDA team
MetY protein sequence
SwissProt
Manually annotated by BRENDA team
putative
UniProt
Manually annotated by BRENDA team
wild-type, strain me-2 and me-7, methionineless mutants
-
-
Manually annotated by BRENDA team
FM518
-
-
Manually annotated by BRENDA team
FM518
-
-
Manually annotated by BRENDA team
fission yeast, IFO-0363
-
-
Manually annotated by BRENDA team
strain HD4
AY257545
GenBank
Manually annotated by BRENDA team
strain HD4
AY257545
GenBank
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
-
wild-type cells are able to grow on both methanethiol and dimethyldisulfide as sole sulfur sources. Both sulfur compounds are incorporated as an entire molecule, adding the terminal S-CH3 group to O-acetylhomoserine. In this reaction, methionine is directly formed. the reaction is catalyzed by O-acetylhomoserine sulfhydrylase MetY. The deletion of metY results in methionine auxotrophic strains grown on methanethiol or dimethyldisulfide as sole sulfur sources. In vitro studies with the wild-type reveal a relatively low activity of MetY for methanethiol and dimethyldisulfide
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2 O-acetyl-L-homoserine + dimethyldisulfide
2 L-methionine + 2 acetate
show the reaction diagram
-
dimethyldisulfide may be reductively cleaved into methanethiol prior to assimilation
-
-
?
2 O-acetyl-L-homoserine + H2S
2 L-homocysteine + 2 acetate
show the reaction diagram
-
-
-
-
?
L-cysteine + KCN
?
show the reaction diagram
L-glutamic acid + KCN
?
show the reaction diagram
L-glutamine + KCN
?
show the reaction diagram
L-homocysteine + KCN
gamma-cyano-alpha-aminobutyric acid + H2S
show the reaction diagram
L-homoserine + H2S
homocysteine + ?
show the reaction diagram
L-homoserine + H2S
L-homocysteine + H2O
show the reaction diagram
lesser activity
-
-
?
L-homoserine + KCN
?
show the reaction diagram
-
inactive
-
-
?
L-serine + H2S
L-cysteine + H2O
show the reaction diagram
lesser activity
-
-
?
L-serine + KCN
?
show the reaction diagram
-
inactive
-
-
?
L-serine-O-sulfate + Se2-
L-selenocystine + ?
show the reaction diagram
-
-
-
-
?
O-acetyl-L-homoserine + 2-mercaptoethanol
?
show the reaction diagram
o-acetyl-L-homoserine + CN-
gamma-cyano-alpha-aminobutyric acid + acetate
show the reaction diagram
O-acetyl-L-homoserine + ethanol
O-ethyl-homoserine + acetic acid
show the reaction diagram
O-acetyl-L-homoserine + ethyl mercaptan
L-ethionine + acetic acid
show the reaction diagram
o-acetyl-L-homoserine + H2S
L-homocysteine + acetate
show the reaction diagram
O-acetyl-L-homoserine + H2S
L-homocysteine + acetic acid
show the reaction diagram
o-acetyl-L-homoserine + KCN
gamma-cyano-alpha-aminobutyric acid + acetate
show the reaction diagram
-
-
-
-
?
O-acetyl-L-homoserine + methanethiol
L-methionine + acetate
show the reaction diagram
O-acetyl-L-homoserine + methanethiol
L-methionine + acetic acid
show the reaction diagram
O-acetyl-L-homoserine + methanol
O-methyl-homoserine + acetic acid
show the reaction diagram
Corynebacterium acetophilum
-
-
-
?
O-acetyl-L-homoserine + methyl mercaptan
L-methionine + acetic acid
show the reaction diagram
O-acetyl-L-homoserine + methylselenide
seleno-L-methionine + acetic acid
show the reaction diagram
O-acetyl-L-homoserine + n-butanol
O-butyl-homoserine + acetic acid
show the reaction diagram
O-acetyl-L-homoserine + n-pentanol
O-pentyl-homoserine + acetic acid
show the reaction diagram
Corynebacterium acetophilum
-
-
-
?
O-acetyl-L-homoserine + n-propanol
O-propyl-homoserine + acetic acid
show the reaction diagram
O-acetyl-L-homoserine + S2-
L-homocysteine + acetic acid
show the reaction diagram
-
physiological substrate NaHS
-
-
-
O-acetyl-L-homoserine + Se2-
L-selenohomocystine + ?
show the reaction diagram
-
-
-
-
?
O-acetyl-L-homoserine + thioglycerol
?
show the reaction diagram
O-acetyl-L-homoserine + thioglycolic acid
?
show the reaction diagram
o-acetyl-L-serine + H2S
L-cysteine + acetate
show the reaction diagram
lesser activity
-
-
?
O-acetyl-L-serine + H2S
L-cysteine + acetic acid
show the reaction diagram
O-acetyl-L-serine + H2S
S-methylcysteine + ?
show the reaction diagram
-
-
-
?
o-acetyl-L-serine + KCN
?
show the reaction diagram
-
inactive
-
-
?
O-acetyl-L-serine + methanethiol
?
show the reaction diagram
-
reaction only in phosphate buffer, relative activity compared to O-acetyl-L-homoserine 14.8%
-
-
?
O-acetyl-L-serine + methyl mercaptan
S-methylcysteine + ?
show the reaction diagram
-
-
-
?
O-acetyl-L-serine + NaHSe2
L-selenocystine + ?
show the reaction diagram
-
-
-
-
?
O-acetyl-L-serine + S2-
L-cysteine + acetic acid
show the reaction diagram
-
physiological substrate NaHS
-
-
-
O-acetyl-L-serine + Se2-
L-selenocystine + ?
show the reaction diagram
-
-
-
-
?
O-phospho-L-serine + H2S
?
show the reaction diagram
-
-
-
?
o-phospho-L-serine + KCN
?
show the reaction diagram
-
inactive
-
-
?
O-phosphoryl-L-serine + H2S
L-cysteine + H2O
show the reaction diagram
lesser activity
-
-
?
O-succinyl-L-homoserine + H2S
homocysteine + ?
show the reaction diagram
O-succinyl-L-homoserine + H2S
L-homocysteine + succinate
show the reaction diagram
lesser activity
-
-
?
o-succinyl-L-homoserine + KCN
?
show the reaction diagram
-
inactive
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
o-acetyl-L-homoserine + CN-
gamma-cyano-alpha-aminobutyric acid + acetate
show the reaction diagram
o-acetyl-L-homoserine + H2S
L-homocysteine + acetate
show the reaction diagram
O-acetyl-L-homoserine + H2S
L-homocysteine + acetic acid
show the reaction diagram
O-acetyl-L-homoserine + methanethiol
L-methionine + acetate
show the reaction diagram
O-acetyl-L-homoserine + S2-
L-homocysteine + acetic acid
show the reaction diagram
-
physiological substrate NaHS
-
-
-
O-acetyl-L-serine + S2-
L-cysteine + acetic acid
show the reaction diagram
-
physiological substrate NaHS
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pyridoxal 5'-phosphate
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
cyanide ions can be replaced as cosubstrates by hydrogen sulfide, methylmercaptan, ethylmercaptan and phenylmercaptan
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
butanol
Corynebacterium acetophilum
-
-
diethyl N-[[3-bromo-4-([[2,4-diamino-5-(2,3-dibromopropyl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-6-yl]methyl]amino)phenyl]carbonyl]glutamate
-
inhibition of methionine synthase, arrest of cell cycle in G1/S phase and apoptosis. Treatment results in increase in cyclin E and cyclin-dependent kinase 2, reduction of caspase-3, poly(ADP-ribose) polymerase, caspase-8, and caspase-9 protein levels
DL-C-propagylglycine
-
DL-propargylglycine
89% inhibition at 1 mM
hydrazine
Corynebacterium acetophilum
-
-
hydroxylamine
95% inhibition at 1 mM, 76% at 0.1 mM
Hydroxylamine hydrochloride
Isopropanol
Corynebacterium acetophilum
-
-
L-homoserine
L-methionine
L-Penicillamine
methanol
Corynebacterium acetophilum
-
-
methylmercaptan
Corynebacterium acetophilum
-
-
n-Propanol
Corynebacterium acetophilum
-
-
N-[[3-bromo-4-([[2,4-diamino-5-(2,3-dibromopropyl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-6-yl]methyl]amino)phenyl]carbonyl]glutamic acid
-
inhibition of methionine synthase, arrest of cell cycle in G1/S phase and apoptosis. Treatment results in increase in cyclin E and cyclin-dependent kinase 2, reduction of caspase-3, poly(ADP-ribose) polymerase, caspase-8, and caspase-9 protein levels
Na2S
Corynebacterium acetophilum
-
-
O-acetyl-L-serine
O-acetyl-L-threonine
Corynebacterium acetophilum
-
-
O-ethylhomoserine
Corynebacterium acetophilum
-
-
O-phospho-L-serine
-
-
O-succinyl-DL-homoserine
p-chloromercuribenzoate
Corynebacterium acetophilum
-
-
phenylhydrazine
pyridoxal
-
inhibits the activity competitively with respect to pyridoxal 5'-phosphate
S-adenosyl-L-homocysteine
S-adenosyl-L-methionine
Semicarbazide
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
dithiothreitol
-
2 mM, catalytic activity 124%
DL-cystathionine
-
10 mM addition, AHS activity 105%
ferricyanide
-
1 mM, catalytic activity 102-119%
pyridoxal 5'-phosphate
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
40
ethanol
Corynebacterium acetophilum
-
-
0.053 - 2.4
H2S
4.17
L-homocysteine
-
at 45°C, pH 7.5
10.4
L-homoserine
-
-
4
L-serine-O-sulfate
-
NaHS or Na2Se as donor
0.8
methyl-mercaptan
-
-
10
Na2Se
-
L-serine-O-sulfate as acceptor
1.2
NaHSe
-
L-serine-O-sulfate as acceptor
1.1 - 13
O-acetyl-L-homoserine
2.5 - 5.12
O-acetyl-L-serine
11.1
O-succinyl-L-homoserine
-
-
0.52 - 0.7
S2-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
16
L-homoserine
-
-
0.9 - 15
L-methionine
57 - 70
NaHS
21.8
O-acetyl-L-serine
-
-
19
O-succinyl-DL-homoserine
-
-
0.01
S-adenosylmethionine
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.01
diethyl N-[[3-bromo-4-([[2,4-diamino-5-(2,3-dibromopropyl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-6-yl]methyl]amino)phenyl]carbonyl]glutamate
Homo sapiens
-
pH 7.2, 37°C
0.0014
N-[[3-bromo-4-([[2,4-diamino-5-(2,3-dibromopropyl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-6-yl]methyl]amino)phenyl]carbonyl]glutamic acid
Homo sapiens
-
pH 7.2, 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0272
-
cell-free extract
0.0479
-
after heat treatment
0.06
cysthathione beta-lyase reaction
0.108
Corynebacterium acetophilum
-
O-alkylhomoserine synthesizing activity
0.37
-
after DEAE-cellufine A-500m treatment
0.58
L-homoserine as substrate
0.72
O-succinyl-L-homoserine as substrate
1.02
-
substrate O-acetyl-L-serine
1.33
L-serine as substrate
1.57
O-phospho-L-serine as substrate
2.12
O-acetyl-L-serine as substrate
3.17
crude extract
4.2
-
O-acetylhomoserine sulfhydrylation
6.88
-
substrate O-acetyl-L-homoserine
7.45
-
mutant strain No. 17, O-acetylhomoserine sulfhydrylase activity
7.7
-
O-acetylhomoserine methylsulfhydrylation
14.3
after heat treatment at 65°C
14.5
-
after Phenyl-Toyopearl 650M treatment
16.7
Corynebacterium acetophilum
-
O-acetylhomoserine sulfhydrylase activity
17.2
-
after sephacryl S-200 HR treatment
28.3
-
mutant strain No. 17, O-acetylserine sulfhydrylase activity
29.9
-
recombinant enzyme purified from Escherichia coli
36
Q Sepharose pool
40.7
recombinant enzyme
49.82
O-acetyl-L-homoserine as substrate
61
-
substrate dimethyldisulfide, pH 7.8, 30°C
63
-
substrate methanethiol, pH 7.8, 30°C
67.7
phenyl Sepharose pool
480
-
substrate H2S, pH 7.8, 30°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.5
Corynebacterium acetophilum
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 12
50% maximum activity at pH 6.3 and pH 9.3
6.3 - 8.8
less than 50% activity above and below
6.6 - 8.5
-
50% activity at pH 6.6, 90% activity at pH 7.5 and 8.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
42 - 45
Corynebacterium acetophilum
-
-
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.02
AY257545
calculated from amino acid sequence
PDB
SCOP
CATH
ORGANISM
UNIPROT
Campylobacter jejuni subsp. jejuni serotype O:2 (strain ATCC 700819 / NCTC 11168)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
34670
AY257545
calculated from amino acid sequence
44160
calculated from amino acid sequence
46000
4 * 46000, calculated from OAH1 sequence
46059
4 * 46059, calculated from amino acid sequence
46850
-
calculated from amino acid sequence
47000
4 * 47000, SDS-PAGE
51000
-
4 * 51000, SDS-PAGE
57000
-
4 * 57000, gel filtration in presence of urea and beta-mercaptoethanol
96000
-
sucrose density gradient centrifugation , wild-type, O-acetylserine sulfhydrylase activity
99000
-
gel filtration, sucrose density gradient centrifugation , mutant strain No. 17, O-acetylserine sulfhydrylase activity
110000
Corynebacterium acetophilum
-
2 * 110000, SDS-PAGE
163000
gel filtration
170000
-
sucrose density gradient ultracentrifugation
180000
-
gel filtration
182000
-
gel filtration, mutant strain No. 17, sucrose density gradient centrifugation, O-acetylhomoserine sulfhydrylase activity
186000
-
gel filtration
190000
gel filtration
194000
-
sucrose density gradient centrifugation, wild-type, OAS-OAH sulfhydrylase with O-acetylserine as substrate
196000
-
sucrose density gradient centrifugation, wild-type, OAS-OAH sulfhydrylase with O-acetylhomoserine as substrate
200000
-
gel filtration, sucrose density gradient centrifugation
220000
Corynebacterium acetophilum
-
gel filtration
250000 - 260000
-
gel filtration
267000
-
gel filtration
360000
-
gel filtration
480000
-
gel filtration, larger than, no correct value could be estimated
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hexamer
monomer
tetramer
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
to 2.1 A resolution, space group P21
to 2.2 A resolution, space group C2, two monomers per asymmetric unit. The monomer adopts an alpha/beta fold and consists of a large central seven-stranded beta-sheet, a two-stranded beta-sheet and a three-stranded beta-sheet. The beta-sheets are flanked by a total of 12 alpha-helices and two 3(10)-helices. The active site is located near the N-terminus of alpha3. The pydridoxal 5'-phosphate-binding site is occupied by water molecules in the absence of the cofactor. The phosphate group of pydridoxal 5'-phosphate makes hydrogen bonds to Thr204, Ser202 and the amide N-atoms of Gly83 and Met84. Asp180 is within salt-bridge distance of the N1 atom of pydridoxal 5'-phosphate. Leu353, Met183, Ile87 and Met84 interact with the hydrophobic region of pydridoxal 5'-phosphate
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 10.5
-
stable on incubation at 60°C for 30 min
662480
7
-
optimal pH for stability
637834
7 - 12
-
661358
7.8 - 8
-
most stable at
637825
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
more stable at 30°C than at 0°C
40 - 65
-
activity decreases at about 40°C and is completely lost at 65°C
60
-
stable at
additional information
-
no loss of activity after incubation at temperatures up to 60°C for 30 min at pH 7.5
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
enzyme appears to be quite stable
-
enzyme remains stable after purification, no dilution inactivation is observed
-
existence of glycerol in the purification buffer keeps the enzyme very stable, sensitive to salts such as (NH4)2SO4 and NaCl in absence of glycerol
-
not stable even in presence of a cofactor
Corynebacterium acetophilum
-
sensitive to trypsin digestion
-
very unstable, can be stabilized by addition of 25% sucrose or glycerol
-
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
urea
-
denatured by 2.0 M urea
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15°C, 80% of the activity remains after storage for 6 months
-
-20°C, can be stored without any loss of activity
-
-20°C, can be stored without loss of catalytic activity
-
-20°C, stable for at least 1 week, stable for at least 6 weeks if stabilized by addition of 20% glycerol
-
-20°C, stable for at least 6 months
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Nicotiana tabacum
-
expression in Escherichia coli
MET17/MET25 gene cloned and overexpressed in Escherichia coli
-
MetY gene can complement the metB mutant of Escherichia coli
oah1 gene cloned, sequenced and overexpressed in Escherichia coli BL21(DE3)
overexpression in Escherichia coli
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
synthesis
-
overexpression of gene metY increases the in vitro activity of O-acetylhomoserine aminocarboxypropyltransferase to 1780 mU/mg and is beneficial for methionine production, since the intracellular methionine pool increases 2fold in the engineered strain
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