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Information on EC 2.5.1.61 - hydroxymethylbilane synthase
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2.5.1.61 hydroxymethylbilane synthaseIUBMB Comments
The enzyme works by stepwise addition of pyrrolylmethyl groups until a hexapyrrole is present at the active centre. The terminal tetrapyrrole is then hydrolysed to yield the product, leaving a cysteine-bound dipyrrole on which assembly continues. In the presence of a second enzyme, EC 4.2.1.75 uroporphyrinogen-III synthase, which is often called cosynthase, the product is cyclized to form uroporphyrinogen-III. If EC 4.2.1.75 is absent, the hydroxymethylbilane cyclizes spontaneously to form uroporphyrinogen I.
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Word Map
- 2.5.1.61
- porphyria
-
intermittent
- heme
- aip
- erythrocyte
-
delta-aminolevulinic
- dehydratase
- protoporphyrin
-
erythroid
- urinary
- gapdh
-
5-aminolevulinic
-
normfinder
-
ferrochelatase
-
housekeeping
-
genorm
- coproporphyrinogen
-
bestkeeper
-
ywhaz
-
abdominal
-
neurovisceral
- tetrapyrrole
-
asymptomatic
-
erythroid-specific
-
photodynamic
-
half-normal
- protoporphyrinogen
-
porphyrinogenic
- variegate
- coproporphyria
- diagnostics
-
lightcycler
-
proto
- medicine
-
hyponatremia
-
cutanea
-
non-erythroid
- pharmacology
-
gata-1
- beta-globin
-
beta-2-microglobulin
-
rpl13a
- tarda
The enzyme appears in viruses and cellular organisms
Synonyms
(HMB)-synthase, AN0121.3, EC 4.3.1.8, HemC, hepatic porphobilinogen deaminase, HMB synthase, HMB-S, HMBS, HMBS1a-synthase, HMBS1b-synthase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
EC 4.3.1.8
HemC
hepatic porphobilinogen deaminase
HMB-S
HMBS
HMBS1b-synthase
housekeeping, truncated form, GenBank GQ850462, isolated from liver
HMBS2a-synthase
erythroid-specific, GenBank GQ850463, isolated from spleen
HMBS2b-synthase
erythroid-specific, GenBank GQ850464, isolated from spleen
hydroxymethylbilane synthase
PBG deaminase
PBG-D
PBG-deaminase
PBGD
porphobilinogen ammonia-lyase (polymerizing)
-
-
-
-
porphobilinogen deaminase
pre-uroporphyrinogen synthase
-
-
-
-
preuroporphyrinogen synthetase
synthase, uroporphyrinogen I
-
-
-
-
UPGI-S
uroporphyrinogen I synthase
uroporphyrinogen I synthetase
uroporphyrinogen synthase
-
-
-
-
uroporphyrinogen synthetase
EC 4.3.1.8
-
-
formerly
-
porphobilinogen deaminase
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
4 porphobilinogen + H2O = hydroxymethylbilane + 4 NH3
The enzyme works by stepwise addition of pyrrolylmethyl groups until a hexapyrrole is present at the active centre. The terminal tetrapyrrole is then hydrolysed to yield the product, leaving a cysteine-bound dipyrrole on which assembly continues. In the presence of a second enzyme, EC 4.2.1.75 uroporphyrinogen-III synthase, which is often called cosynthase, the product is cyclized to form uroporphyrinogen-III. If EC 4.2.1.75 is absent, the hydroxymethylbilane cyclizes spontaneously to form uroporphyrinogen I
-
-
-
4 porphobilinogen + H2O = hydroxymethylbilane + 4 NH3
mechanism
-
4 porphobilinogen + H2O = hydroxymethylbilane + 4 NH3
catalytic cycle, cofactor assembly and tetrapyrrole chain polymerization mechanism, C261 is involved, residues D99 and R167 are essential for activity, overview
-
4 porphobilinogen + H2O = hydroxymethylbilane + 4 NH3
four molecules of the pyrrole porphobilinogen are condensed to form the linear tetrapyrrole preuroporphyrinogen (hydroxymethylbilane). Hydrolysis of the linkage between the first substrate moiety and the cofactor releases the tetrapyrrole product preuroporphyrinogen
4 porphobilinogen + H2O = hydroxymethylbilane + 4 NH3
reaction mechanism with active site residues R11, D84 and R176 that appear to be involved in controlling crucial steps during tetrapyrrole, detailed interaction analysis, overview. The compactness of the overall protein decreases progressively with addition of each pyrrole ring. domains move apart while the cofactor turn region moves towards the second domain, thus creating space for the pyrrole rings added at each stage. Residues of the flexible active site loop play a significant role in its modulation. During this movement, loop residue D50 interacts with R149 and K55 interacts with Q243, E305 and V306 with an occupancy of 41% along the trajectory. Upon removal of hydroxymethylbilane, the structure of the enzyme gradually relaxes to resemble its initial stage structure, indicating its readiness to resume a new catalytic cycle
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
elimination
-
-
of NH3, C-N bond cleavage
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
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SYSTEMATIC NAME
IUBMB Comments
porphobilinogen:(4-[2-carboxyethyl]-3-[carboxymethyl]pyrrol-2-yl)methyltransferase (hydrolysing)
The enzyme works by stepwise addition of pyrrolylmethyl groups until a hexapyrrole is present at the active centre. The terminal tetrapyrrole is then hydrolysed to yield the product, leaving a cysteine-bound dipyrrole on which assembly continues. In the presence of a second enzyme, EC 4.2.1.75 uroporphyrinogen-III synthase, which is often called cosynthase, the product is cyclized to form uroporphyrinogen-III. If EC 4.2.1.75 is absent, the hydroxymethylbilane cyclizes spontaneously to form uroporphyrinogen I.
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CAS REGISTRY NUMBER
COMMENTARY
9036-47-9
-
9074-91-3
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
porphobilinogen + H2O
hydroxymethylbilane + 4 NH3
-
polymerization of 4 pyrrole molecules to a linear tetrapyrrole
i.e. pre-uroporphyrinogen, highly unstable compound
-
?
4 porphobilinogen + H2O
hydroxymethylbilane + 4 NH3
-
-
-
?
4 porphobilinogen + H2O
hydroxymethylbilane + 4 NH3
-
-
-
?
porphobilinogen
?
-
-
-
-
-
porphobilinogen
?
-
-
-
-
-
porphobilinogen + H2O
1-hydroxymethylbilane + 4 NH3
-
third reaction step in heme biosynthesis pathway
-
-
?
porphobilinogen + H2O
1-hydroxymethylbilane + 4 NH3
-
polymerization of 4 pyrrole molecules to a linear tetrapyrrole
i.e. pre-uroporphyrinogen, highly unstable compound
-
?
porphobilinogen + H2O
hydroxylmethylbilane + NH3
-
-
1-hydroxymethylbilane, highly unstable
?
porphobilinogen + H2O
hydroxylmethylbilane + NH3
-
-
uroporphyrinogen I
?
porphobilinogen + H2O
hydroxylmethylbilane + NH3
-
-
uroporphyrinogen I
?
porphobilinogen + H2O
hydroxylmethylbilane + NH3
-
stoichiometry of enzyme reaction
-
?
porphobilinogen + H2O
hydroxylmethylbilane + NH3
-
-
uroporphyrinogen I, uroporphyrinogen
?
porphobilinogen + H2O
hydroxylmethylbilane + NH3
-
-
-
?
porphobilinogen + H2O
hydroxylmethylbilane + NH3
-
-
-
?
porphobilinogen + H2O
hydroxylmethylbilane + NH3
-
-
at pH 8.2, uroporphyrinogen I
?
porphobilinogen + H2O
hydroxylmethylbilane + NH3
-
-
uroporphyrinogen I
?
porphobilinogen + H2O
hydroxylmethylbilane + NH3
-
-
-
?
porphobilinogen + H2O
hydroxylmethylbilane + NH3
-
-
at pH 8.2, uroporphyrinogen I
?
porphobilinogen + H2O
hydroxylmethylbilane + NH3
-
-
uroporphyrinogen
?
porphobilinogen + H2O
hydroxymethylbilane + NH3
-
-
-
-
?
porphobilinogen + H2O
hydroxymethylbilane + NH3
-
enzyme defects are involved in acute intermittent porphyria, AIP
-
-
?
porphobilinogen + H2O
hydroxymethylbilane + NH3
-
enzyme defects are involved in acute intermittent porphyria, AIP, a neuropathic disease
-
-
?
porphobilinogen + H2O
hydroxymethylbilane + NH3
-
the enzyme is important in heme biosynthesis, a nonsense mutation in the porphobilinogen deaminase gene causes acute intermittent porphyria, AIP, overview, eight enzymes are involved in the heme synthesis and defects in seven of them cause porphyria, overview
-
-
?
porphobilinogen + H2O
hydroxymethylbilane + NH3
the enzyme is important in heme biosynthesis, a nonsense mutation in the porphobilinogen deaminase gene causes chester porphyria, existence of dual porphyrias with two enzymes of heme biosynthesis being deficient simultaneously, overview
-
-
?
porphobilinogen + H2O
hydroxymethylbilane + NH3
-
third step in the heme biosynthetic pathway, enzyme defects are involved in acute intermittent porphyria, AIP, an autosomal dominant disorder characterised by acute, potentially life-threatening neurological attacks that are precipitated by various drugs, reproductive hormones and other factors
-
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
uroporphyrinogen III cosynthase is more heat-labile than porphobilinogen deaminase. Heat-treatment of the porphobilinogen deaminase/uroporphyrinogen III cosynthase enzyme system forms only 2-4% of uroporphyrinogen III
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
porphobilinogen + H2O
uroporphyrinogen III
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
additional information
?
-
-
third enzyme in the heme biosynthetic pathway
-
-
-
additional information
?
-
-
in presence of a second enzyme, EC 4.2.1.75, uroporphyrinogen-III synthase, often called co-synthase, the product is cyclized to form uroporphyrinogen-III
-
-
-
additional information
?
-
-
enzyme from chloroplasts is a nuclear-encoded protein, contains a transit-peptide part for transport across the organelle membrans
-
-
-
additional information
?
-
-
third enzyme in the heme biosynthetic pathway
-
-
-
additional information
?
-
-
third enzyme in the heme biosynthetic pathway
-
-
-
additional information
?
-
-
third enzyme in the heme biosynthetic pathway
-
-
-
additional information
?
-
-
third enzyme in the heme biosynthetic pathway
-
-
-
additional information
?
-
-
occurrence of multiple forms of the enzyme. These isomers correspond to the enzyme-substrate intermediates: mono-, di-, tri-, and tetrapyrrole
-
-
-
additional information
?
-
-
mutations of the residues R167, R173, R149, and D99 of the enzyme cause acute intermittent porphyria, overview
-
-
-
additional information
?
-
-
recurrent mutations G111R and R173Q occurring at CpG motifs of the enzyme cause acute intermittent porphyria AIP, a disorder of the heme biosynthetic pathway, oerview
-
-
-
additional information
?
-
-
safety, pharmacokinetics and pharmacodynamics of recombinant human porphobilinogen deaminase P 9808, administered to healthy subjects and asymptomatic porphobilinogen deaminase-deficient subjects with high concentrations of porphobilinogen, the substrate of porphobilinogen deaminase for investigation and establishing of an alternative therapy of acute intermittent porphyria, AIP, method, overview
-
-
-
additional information
?
-
-
the enzyme is also active in uroporphyrinogen formation from porphobilinogen, cf. EC 4.2.1.75
-
-
-
additional information
?
-
-
enzyme-intermediates with increasing number of porphobilinogen molecules are formed during the catalysis of enzyme HMBS
-
-
-
additional information
?
-
-
third enzyme in the heme biosynthetic pathway
-
-
-
additional information
?
-
-
third enzyme in the heme biosynthetic pathway
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
porphobilinogen + H2O
1-hydroxymethylbilane + 4 NH3
-
third reaction step in heme biosynthesis pathway
-
-
?
4 porphobilinogen + H2O
hydroxymethylbilane + 4 NH3
-
-
-
?
4 porphobilinogen + H2O
hydroxymethylbilane + 4 NH3
-
-
-
?
porphobilinogen
?
-
-
-
-
-
porphobilinogen
?
-
-
-
-
-
porphobilinogen + H2O
hydroxymethylbilane + NH3
-
enzyme defects are involved in acute intermittent porphyria, AIP
-
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?
porphobilinogen + H2O
hydroxymethylbilane + NH3
-
enzyme defects are involved in acute intermittent porphyria, AIP, a neuropathic disease
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-
?
porphobilinogen + H2O
hydroxymethylbilane + NH3
-
the enzyme is important in heme biosynthesis, a nonsense mutation in the porphobilinogen deaminase gene causes acute intermittent porphyria, AIP, overview, eight enzymes are involved in the heme synthesis and defects in seven of them cause porphyria, overview
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-
?
porphobilinogen + H2O
hydroxymethylbilane + NH3
the enzyme is important in heme biosynthesis, a nonsense mutation in the porphobilinogen deaminase gene causes chester porphyria, existence of dual porphyrias with two enzymes of heme biosynthesis being deficient simultaneously, overview
-
-
?
porphobilinogen + H2O
hydroxymethylbilane + NH3
-
third step in the heme biosynthetic pathway, enzyme defects are involved in acute intermittent porphyria, AIP, an autosomal dominant disorder characterised by acute, potentially life-threatening neurological attacks that are precipitated by various drugs, reproductive hormones and other factors
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?
additional information
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third enzyme in the heme biosynthetic pathway
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-
-
additional information
?
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in presence of a second enzyme, EC 4.2.1.75, uroporphyrinogen-III synthase, often called co-synthase, the product is cyclized to form uroporphyrinogen-III
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-
-
additional information
?
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enzyme from chloroplasts is a nuclear-encoded protein, contains a transit-peptide part for transport across the organelle membrans
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-
-
additional information
?
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third enzyme in the heme biosynthetic pathway
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-
additional information
?
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third enzyme in the heme biosynthetic pathway
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-
additional information
?
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third enzyme in the heme biosynthetic pathway
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-
additional information
?
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third enzyme in the heme biosynthetic pathway
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additional information
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occurrence of multiple forms of the enzyme. These isomers correspond to the enzyme-substrate intermediates: mono-, di-, tri-, and tetrapyrrole
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additional information
?
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mutations of the residues R167, R173, R149, and D99 of the enzyme cause acute intermittent porphyria, overview
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additional information
?
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recurrent mutations G111R and R173Q occurring at CpG motifs of the enzyme cause acute intermittent porphyria AIP, a disorder of the heme biosynthetic pathway, oerview
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additional information
?
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safety, pharmacokinetics and pharmacodynamics of recombinant human porphobilinogen deaminase P 9808, administered to healthy subjects and asymptomatic porphobilinogen deaminase-deficient subjects with high concentrations of porphobilinogen, the substrate of porphobilinogen deaminase for investigation and establishing of an alternative therapy of acute intermittent porphyria, AIP, method, overview
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additional information
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the enzyme is also active in uroporphyrinogen formation from porphobilinogen, cf. EC 4.2.1.75
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additional information
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third enzyme in the heme biosynthetic pathway
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additional information
?
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third enzyme in the heme biosynthetic pathway
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
dipyrromethane
-
cofactor assembly mechanism, R149 and R173 are important, cofactor is produced from the apo-enzyme with pre-uroporphyrinogen
dipyrromethane
the active site possesses the unusual dipyrromethane cofactor which is extended during the reaction by the sequential addition of the four substrate molecules. The cofactor is linked covalently to the enzyme through a thioether bridge to the invariant Cys254, binding structure, overview. Hydrolysis of the linkage between the first substrate moiety and the cofactor releases the tetrapyrrole product preuroporphyrinogen. The dipyrromethane cofactor of enzyme PBGD is light-sensitive
dipyrromethane
-
the enzyme possesses a dipyrromethane cofactor, which is covalently linked by a thioether bridge to the invariant cysteine residue, Cys241. The cofactor extends during the reaction by the sequential addition of the four substrate molecules, which are released as a linear tetrapyrrole product. Structure determination of the oxidized form of the dipyrromethane cofactor covalently attached to Cys241, overview. Analysis of oxidation states of the dipyrromethane cofactor and a proposed mechanism for oxidation of the dipyrromethane to dipyrromethene and subsequently dipyrromethanone
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
protoporphyrin IX
-
enzyme activity decreases with increasing concentrations, reaching a 33% inhibition at the vivo concentration of porphyrin, 0.00185 mM, and 0.014 mM porphobilinogen
protoporphyrinogen
-
inhibits both erythroid and lymphoblast forms of the enzyme
Hg2+
-
inhibition by mercury derivates of porphobilinogen, i.e. PBG-Hg, and opsopyrroledicarboxylic acid, i.e. OPD-Hg, is enhanced by porphobilinogen; opsopyrroledicarboxylic acid enhances inhibition by HgCl2
p-hydroxymercuribenzoate
-
i.e. PHMB, inhibition is enhanced by porphobilinogen
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.051
Hydroxymethylbilane
-
porphobilinogen deaminase/uroporphyrinogen III cosynthase enzyme system
0.00342
porphobilinogen
-
mutant Q204K, Vmax is reduced 3fold to 0.66 nmol/min compared to the wild type, 50 mM Tris-HCl, pH 8.2
0.0042
porphobilinogen
-
wild type enzyme, in 50 mM Tris, 0.1% BSA, 0.1% Triton, pH 8.2, at 37°C
0.00445
porphobilinogen
-
wild type, Vmax = 2.14 nmol/min, 50 mM Tris-HCl, pH 8.2
0.0066
porphobilinogen
-
mutant enzyme T59I, in 50 mM Tris, 0.1% BSA, 0.1% Triton, pH 7.8, at 37°C
0.016
porphobilinogen
wild type enzyme, at 37°C in Tris-HCl buffer (100 mM, pH 8.0, containing 0.15 mg/ml BSA)
0.046
porphobilinogen
-
porphobilinogen deaminase/uroporphyrinogen III cosynthase enzyme system
0.066
porphobilinogen
mutant enzyme E63A, at 37°C in Tris-HCl buffer (100 mM, pH 8.0, containing 0.15 mg/ml BSA)
0.07
porphobilinogen
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mutant enzyme V215M, in 50 mM Tris, 0.1% BSA, 0.1% Triton, pH 8.0, at 37°C
0.24
porphobilinogen
mutant enzyme E63A, at 37°C in Tris-HCl buffer (100 mM, pH 8.0, containing 0.15 mg/ml BSA)
1.3
porphobilinogen
recombinant wild type enzyme, 50 mM Tris, pH 7.5 containing 40 mM KCl, 0.8% Triton, 8% glycerol, and 2 mM beta-mercaptoethanol, at 37°C
additional information
additional information
-
no differences in kinetics for the housekeeping and the erythroid enzyme form, overview
-
additional information
additional information
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Michaelis-Menten kinetics for uroporphyrinogen formation
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
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linked assay with HemB, CobA/HemD enzymes in 50 mM Tris-HCl, pH 8.0, 2 hours at 25°C produces precorrin-2 from the substrate aminolaevulinic acid
additional information
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enzyme activity in lymphoblasts from variegate porphyria subjects
additional information
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activity of recombinant wild-type and mutant enzymes in transfected SH-SY5Y neuroblastoma cells, overview
additional information
hepatic enzyme activity in untreated acute intermittent porphyria mice (2.2 pM uroporphyrin/mg hemoglobin) does not increase with control plasmid (2.1 pM uroporphyrin/mg hemoglobin) but increases upon treatment with a therapeutic plasmid containing the human wild type enzyme (4.7 pM uroporphyrin/mg hemoglobin), the wild type shows 10 pM uroporphyrin/mg hemoglobin activity, hepatic enzyme deficiency is associated with acute porphyria, 37°C, phosphate buffered saline
additional information
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activity determinatin by uroporphyrinogen formation measurement
additional information
erythrocyte enzyme activity in acute intermittent porphyria mice (7.3 pM uroporphyrin/mg hemoglobin) does not improve with bone marrow graft from porphyria mice (5.2 pM uroporphyrin/mg hemoglobin), increases to 12.4 pM uroporphyrin/mg hemoglobin in mice grafted with bone marrow from wild type, wild type has an activity of 16.9 pM uroporphyrin/mg hemoglobin, erythrocyte enzyme deficiency is not associated with acute porphyria, 37°C, phosphate buffered saline
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
7.6
8.2
additional information
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 10
-
pH 6.0: about 15% of maximal activity, pH 10.0: 25% of maximal activity
6 - 8
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pH 6.0: enzyme is rapidly and irreversibly inactivated below, pH 8.0: about 50% of maximal activity
6 - 9
6.2 - 8.4
-
pH 6.2: 50% of maximal activity, pH 8.4: 30% of maximal activity
additional information
additional information
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stoichiometry and kinetic mechanism of the enzyme reaction at different pH values
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
65
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20 - 80
-
10% of maximal activity at 20°C, 8% of maximal activity at 80°C
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
wild type siblings of mutant cats or unrelated wild type cats, porphyric mutant cats type Saskatchewan (c.189dupT = trunkated (premature stop codon 65) L64S), type Massachusetts (c842_844delGAG = delGly281), type Missouris (c.445C>T = R149W), type OregonAR (c250G>A = A84T)
UniProt
brenda
wild-type D3, Sammlung von Algenkulturen, Pflanzenphysiologisches Institiut Universitt Gttingen, Germany
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brenda
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489925, 489926, 489935, 489938, 489941, 489942, 489943, 489945, 489948, 489951, 5882, 5883, 661042, 662579, 672383, 673142, 676352, 677113, 684446, 689025
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brenda
lethally irradiated acute intermittent porphyria type C57BL/6-CD45.2 mice are treated with plasmids containing human enzyme genes, that are expressed in hepatocytes
SwissProt
brenda
wild type, lethally irradiated acute intermittent porphyria mice, porphyria mice injected with bone marrow cells from wild type C57BL/6-CD45.1 mice or from acute intermittent porphyria mice
UniProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
5 multiple enzyme forms from spleen of phenylhydrazine-treated male rats
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
in the chloroplast, the precursor is processed by the removal of an N-terminal transit peptide which is around 60 residues in length
brenda
-
fusion enzyme with yellow fluorescent protein (YFP), transformed in Vicia faba leaves for localization analysis
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
molecular dynamics simulations for determmination of the exit mechanism of hydroxymethylbilane from the enzyme at the end of the catalytic cycle
evolution
-
all enzymes in the family adopt a three-domain fold in which domains 1 and 2 resemble the fold of type II periplasmic binding proteins and the third domain, to which the cofactor is covalently attached, adopts a distinct alpha/beta topology
evolution
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all enzymes in the family adopt a three-domain fold in which domains 1 and 2 resemble the fold of type II periplasmic binding proteins and the third domain, to which the cofactor is covalently attached, adopts a distinct alpha/beta topology
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malfunction
half-maximal activity of the enzyme causes acute intermittent porphyria due to an error of heme biosynthesis; half-maximal activity of the enzyme causes acute intermittent porphyria due to an error of heme biosynthesis; half-maximal activity of the enzyme causes acute intermittent porphyria due to an error of heme biosynthesis
malfunction
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acute intermittent porphyria is characterized by a partial deficiency in the enzyme, the third enzyme in heme biosynthesis
malfunction
enzyme deficiency results in overproduction of porphyrin precursors in acute intermittent porphyria
malfunction
enzyme deficiency results in overproduction of porphyrin precursors in acute intermittent porphyria
malfunction
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camouflage1 (cf1) mutant develops nonclonal, yellow-green sectors in leaves based on bundle sheath cell-specific death, yellow mutant regions show reduced levels of chlorophyll a + b, and total carotenoids, reduced photosynthesis and stomatal conductance compared to wild type and green regions of the mutant, constant light suppresses the cf1 sector formation, sectors only form during a limited time of leaf development, underlying is a decreased enzyme activity and increased levels of the substrate in green and yellow regions, yellow regions show an additional reduction in catalase activity
malfunction
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autosomal dominantly inherited disease acute intermittent porphyria, AIP, is caused by mutations in hydroxymethylbilane synthase, phenotypes, overview
metabolism
the enzyme hydroxymethylbilane synthase catalyses a key early step of the heme and chlorophyll biosynthesis pathways in which four molecules of the monopyrrole porphobilinogen are condensed to form a linear tetrapyrrole
metabolism
the enzyme hydroxymethylbilane synthase catalyses a key early step of tetrapyrrole biosynthesis pathways in which four molecules of the monopyrrole porphobilinogen are condensed to form a linear tetrapyrrole
metabolism
-
hydroxymethylbilane synthase is the third enzyme in the heme biosynthesis pathway
metabolism
porphobilinogen deaminase, an enzyme in the heme biosynthetic pathway, catalyzes the formation of a linear tetrapyrrole product, 1-hydroxymethylbilane, from four units of porphobilinogen
metabolism
-
the enzyme hydroxymethylbilane synthase catalyses a key early step of tetrapyrrole biosynthesis pathways in which four molecules of the monopyrrole porphobilinogen are condensed to form a linear tetrapyrrole; the enzyme hydroxymethylbilane synthase catalyses a key early step of tetrapyrrole biosynthesis pathways in which four molecules of the monopyrrole porphobilinogen are condensed to form a linear tetrapyrrole
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physiological function
overproduction of enzyme in Emericella nidulans promotes reactive nitrogen species tolerance, whereas repression causes growth that is hypersensitive to reactive nitrogen species. Hydroxymethylbilane synthase modulates the reduction of environmental NO and nitrite levels by flavohemoglobin and nitrite reductase
physiological function
porphobilinogen deaminase catalyzes the formation of 1-hydroxymethylbilane, a crucial intermediate in tetrapyrrole biosynthesis, through a step-wise polymerization of four molecules of porphobilinogen, using a unique dipyrromethane cofactor
Show AA Sequence and Transmembrane Helices (28563 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
Escherichia coli (strain K12)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
33000
35000
36000
38000
40000
41000
42000
43000
44000
45000
53000
-
GST-tagged recombinant p.Ala226ProfsX28, removing the GST tag produces a strongly degraded enzyme
68000
36000
-
1 * 36000, SDS-PAGE in the presence and in the absence of 2-mercaptoethanol; 1 * 36000, SDS-PAGE in the presence of beta-mercaptoethanol
42000
-
x * 68000, GST-tagged recombinant enzyme, SDS-PAGE, x * 42000, detagged recombinant enzyme, SDS-PAGE
42000
-
wild type and mutant recombinant enzymes except truncated enyzme p.Ala226ProfsX28
43000
the purified protein appears as a doublet on SDS gel and the faint upper 45 kDa band may be because of the presence of the uncleaved periplasmic localization signal
43000
housekeeping enzyme, SDS-PAGE; housekeeping enzyme, SDS-PAGE
45000
the purified protein appears as a doublet on SDS gel and the faint upper 45 kDa band may be because of the presence of the uncleaved periplasmic localization signal
68000
-
x * 68000, GST-tagged recombinant enzyme, SDS-PAGE, x * 42000, detagged recombinant enzyme, SDS-PAGE
68000
-
glutathione S-transferase (GST)-tagged wild type and recombinant enzymes except p.Ala226ProfsX28
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
additional information
?
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x * 68000, GST-tagged recombinant enzyme, SDS-PAGE, x * 42000, detagged recombinant enzyme, SDS-PAGE
?
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x * 44000, about, recombinant detagged wild-type and mutant enzymes, SDS-PAGE
monomer
-
1 * 36000, SDS-PAGE in the presence of beta-mercaptoethanol
monomer
-
1 * 36000, SDS-PAGE in the presence and in the absence of 2-mercaptoethanol; 1 * 36000, SDS-PAGE in the presence of beta-mercaptoethanol
monomer
-
1 * 36000, SDS-PAGE in the presence and in the absence of 2-mercaptoethanol; 1 * 36000, SDS-PAGE in the presence of beta-mercaptoethanol
-
additional information
three-dimensional structure analysis, molecular modelling, overview
additional information
-
the two enzyme forms can each be separated into three differently charged subforms by Mono Q chromatography
additional information
-
three-dimensional enzyme structure, computer-based structural modeling, overview
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant enzyme with bound cofactor, crystallization in the dark due to light-sensitivity of the cofactor, hanging drop method, mixing of 5 mg/ml protein in 20 mM Tris-HCl, pH 8.0, and 5 mM DTT, with reservoir solution containing 25% w/v PEG 4000, 100 mM sodium citrate, pH 5.6, and 200 mM ammonium sulfate, X-ray diffraction structure determination and analysis at 1.45 A resolution, molecular modelling
purified recombinant detagged enzyme, mixing of 2.5 mg/ml protein with 0.1 M sodium cacodylate, pH 6.5-6.8, 0.2 M magnesium acetate, and 25-30%PEG 8000, room temperature, removal of the His tag is necessary to obtain enzyme crystals, X-ray diffraction structure determination and analysis at 1.46-1.60 A resolution
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purified recombinant detagged enzyme, mixing of 2.5 mg/ml protein with 0.1 M sodium cacodylate, pH 6.5-6.8, 0.2 M magnesium acetate, and 25-30%PEG 8000, X-ray diffraction structure determination and analysis at 1.46-1.60 A resolution
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vapor diffusion method, hanging drops with 20 mM Tris-HCl buffer, pH 8.2, containing 5 mM dithiothreitol and reservoir solution consisting of 0.6 M ammonium sulfate, 1.2 M lithium sulfate, 5% ethylene glycol, 50 mM sodium citrate, pH 5.6, and 50 mM dithiothreitol, diffraction data are collected at -173°C in 30% glycerol cryoprotected protein crystals
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K55Q/K59Q
-
K55Q-K59Q mutant, lower specific activity than the wild-type enzyme
A84T
type OregonAR (c250G>A), autosomal recessive, therefore phenotype is homozygous, about 35% wild type activity; type OregonAR (c250G>A), autosomal recessive, therefore phenotype is homozygous, about 35% wild type activity; type OregonAR (c250G>A), autosomal recessive, therefore phenotype is homozygous, about 35% wild type activity
L64S
c.189dupT mutant type Saskatchewan with duplication that leads to a frameshift and thus to a trunkated enzyme due to a premature stop codon 65 and the exchange L64S, autosomal dominant; c.189dupT mutant type Saskatchewan with duplication that leads to a frameshift and thus to a trunkated enzyme due to a premature stop codon 65 and the exchange L64S, autosomal dominant; c.189dupT mutant type Saskatchewan with duplication that leads to a frameshift and thus to a trunkated enzyme due to a premature stop codon 65 and the exchange L64S, autosomal dominant
R149W
type Missouris (c.445C>T), substitution identical to human mutation but there leading to an nonsense mutation, autosomal dominant, less than 1% wild type activity; type Missouris (c.445C>T), substitution identical to human mutation but there leading to an nonsense mutation, autosomal dominant, less than 1% wild type activity; type Missouris (c.445C>T), substitution identical to human mutation but there leading to an nonsense mutation, autosomal dominant, less than 1% wild type activity
887insA
-
site-directed mutagenesis, the mutant shows reduced expression and subcellular distribution compared to the wild-type enzyme
A226P
D99G
-
site-directed mutagenesis, inactive holo-enzyme mutant existing as a complex with 2 substrate molecules covalently bound to the dipyrromethane cofactor
E250D
G748A
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site-directed mutagenesis, the mutant shows reduced expression and subcellular distribution compared to the wild-type enzyme
G748C
-
site-directed mutagenesis, the mutant shows reduced expression and subcellular distribution compared to the wild-type enzyme
K132N
-
site-directed mutagenesis, the mutant shows no conformational or kinetic defect, no loss in relative activity (97% of wild-type activity) at standard conditions nor change in Vmax and Km. The mutation is not associated to acute intermittent porphyria, AIP
Q204K
-
c.610C>A, exon 10, missense mutation, 46% wild type activity, 50 mM Tris-HCl, pH 8.2, 0.1% bovine serum albumin, 0.1% Triton, pH 8.2, 37°C, 1 h in the dark
R116W
-
site-directed mutagenesis, the mutant shows 0.5% of wild-type activity and defects in conformational stability. The mutation is associated to acute intermittent porphyria, AIP
R149Q
-
site-directed mutagenesis, inactive apo-enzyme which is unable to assemble with the dipyrromethane cofactor, the mutant enzyme is unstable and heat-labile
R149X
-
identification of a nonsense mutation in the PBGD gene on chromosome 11q23.3, which harbors the mutations causing acute intermittent porphyria, as the underlying genetic defect in Chester porphyria, phenotype, overview
R167Q
R167W
-
site-directed mutagenesis, the mutant shows 4.2% of wild-type activity and defects in enzyme kinetics associated with a very high Km and decreased Vmax. The mutation is associated to acute intermittent porphyria, AIP
R173Q
R173Q/Q204K
-
R173Q is more severe with a resulting enzyme activity of nearly zero, the Q204K increases the negative effect, particularly on the protein stability, 50 mM Tris-HCl, pH 8.2, 0.1% bovine serum albumin, 0.1% Triton, pH 8.2, 37°C, 1 h in the dark
R173W
-
site-directed mutagenesis, the mutant shows 0.6% of wild-type activity and defects in conformational stability and in enzyme kinetics. The mutation is associated to acute intermittent porphyria, AIP
R26C
R26H
-
c.77G>A, exon 3, 0.2% wild type activity, 50 mM Tris-HCl, pH 8.2, 0.1% bovine serum albumin, 0.1% Triton, pH 8.2, 37°C, 1 h in the dark
R73Q/Q204K
-
a complex monoallelic mutation c.[518G>A; c.610C>A] (p.[Arg173Gln;p.Gln204Lys])
T59I
V215E
-
site-directed mutagenesis, the mutant shows 30% of wild-type activity and lower conformational stability and probably a perturbed elongation process, also 70% loss in both activity and Vmax. The mutation is associated to acute intermittent porphyria, AIP
L116K
the specific activity of this recombinant mutant enzyme is 5fold higher than that of the recombinant wild type enzyme, catalyzes the formation of uroporphyrinogen I in addition to uroporphyrinogen III
D44A
specific activity is only about 2% of that of the wild type enzyme
Q200L
mutant lacks the dipyrromethane cofactor and completely loses the catalytic activity
additional information
A226P
-
c.675delA, exon 12, 0.05% wild type activity, small deletion leads to stop codon after 28 completely different amino acids compared to wild type, 50 mM Tris-HCl, pH 8.2, 0.1% bovine serum albumin, 0.1% Triton, pH 8.2, 37°C, 1 h in the dark
E250D
-
c.750A>T, exon 12, missense mutation, 0.5% wild type activity, 50 mM Tris-HCl, pH 8.2, 0.1% bovine serum albumin, 0.1% Triton, pH 8.2, 37°C, 1 h in the dark
R167Q
-
site-directed mutagenesis, mutation of active site residue, highly reduced activity compared to the wild-type enzyme, formation of stable enzyme-intermediate complexes
R167Q
-
8.5% activity, reduced pH optimum from 8.0 to 6.0, accumulates long-lived intermediate complexes
R173Q
-
site-directed mutagenesis, highly reduced activity compared to the wild-type enzyme, the major part of the enzyme exists as apo-enzyme without assembled dipyrromethane cofactor
R173Q
-
c.518G>A, exon 10, missense mutation, 0.15% wild type activity, 50 mM Tris-HCl, pH 8.2, 0.1% bovine serum albumin, 0.1% Triton, pH 8.2, 37°C, 1 h in the dark
R26C
-
c.76C>T, exon 3, 0.3% wild type activity, 50 mM Tris-HCl, pH 8.2, 0.1% bovine serum albumin, 0.1% Triton, pH 8.2, 37°C, 1 h in the dark
additional information
-
all, six, methionine residues are replaced by SeMet
additional information
4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, accumulation of substrates, mutations affect housekeeping and erythroid-specific isozymes in the same way; 4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, mutations affect housekeeping and erythroid-specific isozymes in the same way; 4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, mutations affect housekeeping and erythroid-specific isozymes in the same way; type Massachusetts, in-frame 3 bp deletion (c.842_844delGAG = delGly281), autosomal dominant, less than 1% wild type activity; type Massachusetts, in-frame 3 bp deletion (c.842_844delGAG = delGly281), autosomal dominant, less than 1% wild type activity; type Massachusetts, in-frame 3 bp deletion (c.842_844delGAG = delGly281), autosomal dominant, less than 1% wild type activity
additional information
4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, accumulation of substrates, mutations affect housekeeping and erythroid-specific isozymes in the same way; 4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, mutations affect housekeeping and erythroid-specific isozymes in the same way; 4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, mutations affect housekeeping and erythroid-specific isozymes in the same way; type Massachusetts, in-frame 3 bp deletion (c.842_844delGAG = delGly281), autosomal dominant, less than 1% wild type activity; type Massachusetts, in-frame 3 bp deletion (c.842_844delGAG = delGly281), autosomal dominant, less than 1% wild type activity; type Massachusetts, in-frame 3 bp deletion (c.842_844delGAG = delGly281), autosomal dominant, less than 1% wild type activity
additional information
4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, accumulation of substrates, mutations affect housekeeping and erythroid-specific isozymes in the same way; 4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, mutations affect housekeeping and erythroid-specific isozymes in the same way; 4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, mutations affect housekeeping and erythroid-specific isozymes in the same way; type Massachusetts, in-frame 3 bp deletion (c.842_844delGAG = delGly281), autosomal dominant, less than 1% wild type activity; type Massachusetts, in-frame 3 bp deletion (c.842_844delGAG = delGly281), autosomal dominant, less than 1% wild type activity; type Massachusetts, in-frame 3 bp deletion (c.842_844delGAG = delGly281), autosomal dominant, less than 1% wild type activity
additional information
-
the mutations of the enzyme cause acute intermittent porphyria
additional information
-
analysis of naturally occurring mutations causing acute intermittent porphyria, e.g. recurrent mutations G111R and R173Q occurring at CpG motifs from different patients, countries of origin, overview, haplotype analysis, polymorphism analysis, microsatellite marker analysis, oerview
additional information
-
identification of a mutation in the porphobilinogen deaminase gene in a Slovak acute intermittent porphyria patient, phenotype, the recombinantly expressed mutant enzyme shows 0.18% of wild-type activity, overview
additional information
-
mutations involved in acute intermittent porphyria, AIP, lead to an inactivation of the mutant enzyme, the mutations influence the structure and function of the enzyme
additional information
-
the commonly known variations g.-64T/C (rs589925), g.3581A/G (rs17075), g.6479T/G (rs1131488), and g.7064C/A (rs1784304) are detected by the high-resolution melting method, and also the identified DNA alternations c.76C>T (p.Arg26Cys), c.77G>A (p.Arg26His), c.95G>C (p.Arg32Pro), c.176C>T (p.Thr59Ille), a complex monoallelic mutation c.[518G>A; c.610C>A] (p.[Arg173Gln;p.Gln204Lys]), c.675delA (p.Ala226ProfsX28), c.750A>T (p.Glu250Asp), c.771+1G>T (r.spl?), c.965_966insA (p.Asn322LysfsX36), and c.972_973insG (p.Arg325AlafsX33) can be identified, additionally the alterations g.2922T>G, g.3059G>A, g.3119T/G (rs1006195), c.70G>A (p.Gly24Ser), c.87+5G>T (r.spl?), c.[518G>A;c.610C>A] (p.[Arg173Gln, p.Gln204Lys]), g.7175A>G, c.899_900delinsTGCCTGCATCTG (p.His300LeuFsX10), g.7998G/A (rs1799997) are identified in 97 subjects
additional information
-
previously known mutations that are identified by molecular analysis of the hydroxymethylbilane synthase gene are c.76C>T (R26Cys), c.77G>A (R26H), c.518G>A (R173Q), c.771 + 1G>T (causing donor splice site defect, deletion of exon 12), novel mutations are c.610C>A (Q204K), c.675delA (A226P with stop codon 28), c.750A>T (E250D), one patient shows double mutation of R173Q and Q204K
additional information
disruption in one allele and partial disruption of other allele lead to 25-30% activity compared to wild type
additional information
disruption in one allele and partial disruption of other allele lead to 25-30% activity compared to wild type
additional information
-
4 insertion allels (m1-m4) of camouflage1 (cf1) mutant, mutant develops nonclonal, yellow-green sectors in leaves based on bundle sheath cell-specific death, yellow mutant regions show reduced levels of chlorophyll a + b, and total carotenoids, reduced photosynthesis and stomatal conductance compared to wild type and green regions of the mutant, constant light suppresses the cf1 sector formation, sectors only form during a limited time of leaf development, underlying is a decreased enzyme activity and increased levels of the substrate in green and yellow regions, yellow regions show an additional reduction in catalase activity
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37 - 80
the enzyme loses very little activity even when heated to 80°C and then assayed at 37°C
50
A84T mutant houskeeping enzyme (OregonAR cat) at pH 8.0 has a prolonged half-life of 6.9 h compared to 1.9 h for the wild-type; A84T mutant houskeeping enzyme (OregonAR cat) at pH 8.0 has a prolonged half-life of 6.9 h compared to 1.9 h for the wild-type
60
65
70
additional information
60
only a little loss of activity is found even after 1 h preincubation at 60°C
60
-
during early stages of purification enzyme may be heated with no loss of activity. Inactivation is quite rapid above
65
-
at pH 8.2, wild type with 30% activity loss after 240 min, mutant Q204K with a half-life of 100 min has about one third of the stability of the wild type
additional information
-
the thermostability of the enzyme increases when the dipyrromethane cofactor binds to the apoenzyme and the holoenzyme is formed. A decrease in thermal stability is measured concomitant to elongation of the pyrrole chain, indicating a loosening of the structure prior to product release
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
enzyme is most stable in 0.3 M LiBr, 0.1 M 2-mercaptoethanol, 30% glycerol, 0.15 M Tris chloride, pH 8.0 to 9.0, or 0.3 M (NH4)2SO4
-
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OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
photooxidation of the enzyme in the presence of methylene blue, 0.03%, and roes bengal, 0.03%, over a 5 min period, inhibits 90% and 60% of the enzyme activity, respectively
-
5883
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, forms A to E, stable for up to 18 months in 10 mM potassium phosphate buffer, pH 8.0, containing 0.2 mM dithioerythritol
-
-80°C, 50 mM Tris buffer, pH 7.5, 5% glycerol, and 5 mM beta-mercaptoethanol, 1 year, remains stable
4°C, 50 mM Tris buffer, pH 7.5, 5% glycerol, and 5 mM beta-mercaptoethanol, 1 week, without significant change of activity
erythrocytes lysates stored in 1 mM potassium phosphate, pH 7.6, containing 0.05% Trition X-100, 1 mM dithiothreitol and 1 mM MgCl2, no or little loss of activity after 1 year
-
stored in 0.1 M Tris chloride, pH 8.5, containing 30% glycerol and 0.01 M 2-mercaptoethanol. Under these conditions 50% loss of activity after 3 weeks
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
5 forms, A: native enzyme, B-E: isomeres corresponding to the enzyme-substrate intermediates
-
blood samples are washed in phosphate buffered saline, liver rinsed in phosphate buffered saline
cell harvesting by centrifugation, washed, resuspended in NaCl-phosphate buffer containing of 140 mN NaCl, 2.7 mM KCl, 10 mM Na2HPO4, 1.8 mM KH2PO4, pH 7.3 with protease inhibitor cocktail, and 0.5% Triton X-100, lysis by shaking with lysozyme on ice, sonication, centrifugation, supernatant loaded onto glutathione sepharose 4B column, washed with 20 mM Tris-HCl, 100 mM NaCl, 1 mM EDTA, 0.5% Nonidet P-40+, pH 8.2, proteins eluted in 50 mM Tris-HCl, pH 8.3 buffer with 20 mM glutathione, thrombin digestion with thrombin at 20 U/mg protein at 20°C overnight, addition of glycerol to a concentration of 20%
-
cells centrifuged, washed with 0.9 M NaCl, re-centrifuged, washed with 20 mM Tris-HCl buffer, pH 8.2, with 5 mM dithiothreitol, and 200 microM PMSF, sonication, heating to 60°C under N2 gas, cooled to 4°C, supernatant applied to a Pharmacia 50 K/30 column packed with DEAE-Sephacel anion-exchange resin, equilibrated with 50 mM Tris-HCl buffer, pH 8.2 containing 5 mM dithiothreitol, and 100 microM PMSF, elution with 0-70 mM KCl gradient, active fractions are pooled and concentrated by ultrafiltration with a PM-10 membrane, further concentrated with a Centricon YM-10 centrifugal filter and gel-filtered on a Hiload 16/60 Superdex G-75 column, equilibrated with 100 mM Tris-HCl buffer, pH 8.2, containing 5 mM dithiothreitol and 100 microM PMSF, concentrated with a Centricon YM-10, buffer-exchanged into 20 mM Tris-HCl buffer, pH 8.2, containing 5 mM dithiothreitol with a Pharmacia PD10 column
-
cells harvested and resuspended in 20 mM Tris-HCl buffer, pH 8.0 containing 500 mM NaCl and 10 mM imidazole, cells are lysed by sonication and centrifuged, applied to NiCl2 Sepahrose resin and eluted with buffer and 500 mM imidazole, pooled, concentrated by ultra centrifugation (10 kDa), buffer exchanged with 50 mM Tris-HCl, pH 8.0, with a PD10 column
-
leaves of 8 week old field grown plants are ground in liquid nitrogen and extracted with 25 mM NaP buffer, pH 8.0, containing 1 mM EDTA, 5 mM DTT, and 0.5 mM phenylmethanesulfonylfluoride, centrifuged, supernatant taken for enzyme assay
-
packed red blood cells are washed in phosphate buffered saline, lysed with buffer containing 0.1 M KHEPES, pH 7.5, 0.1% Triton X-100, 1 mM DTT, and 0.02% sodium azide, liver and spleen are diced and homogenized in buffer containing 50 mM KHEPES, pH 7.5, 150 mM KCl, 1 mM Na2EDTA, 1 mM DTT, 0.1 mM PMSF, for activity and thermostability experiments enzymes are expressed in Escherichia coli, cells are harvested and resuspended in 50 mM HEPES, pH 7.8, 0.5 M NaCl, 5 mM DTT, 330 microg/ml lysozyme, 5 microg/ml DNAse and RNAse, freeze-thawed 3times in dry-ice/ethanol, centrifuged, adjusted to pH 7.4 and 8.0 with NaOH, incubated at 37°C or 50°C for 1 h; packed red blood cells are washed in phosphate buffered saline, lysed with buffer containing 0.1 M KHEPES, pH 7.5, 0.1% Triton X-100, 1 mM DTT, and 0.02% sodium azide, liver and spleen are diced and homogenized in buffer containing 50 mM KHEPES, pH 7.5, 150 mM KCl, 1 mM Na2EDTA, 1 mM DTT, 0.1 mM PMSF, for activity and thermostability experiments enzymes are expressed in Escherichia coli, cells are harvested and resuspended in 50 mM HEPES, pH 7.8, 0.5 M NaCl, 5 mM DTT, 330 microg/ml lysozyme, 5 microg/ml DNAse and RNAse, freeze-thawed 3times in dry-ice/ethanol, centrifuged, adjusted to pH 7.4 and 8.0 with NaOH, incubated at 37°C or 50°C for 1 h; packed red blood cells are washed in phosphate buffered saline, lysed with buffer containing 0.1 M KHEPES, pH 7.5, 0.1% Triton X-100, 1 mM DTT, and 0.02% sodium azide, liver and spleen are diced and homogenized in buffer containing 50 mM KHEPES, pH 7.5, 150 mM KCl, 1 mM Na2EDTA, 1 mM DTT, 0.1 mM PMSF, for activity and thermostability experiments enzymes are expressed in Escherichia coli, cells are harvested and resuspended in 50 mM HEPES, pH 7.8, 0.5 M NaCl, 5 mM DTT, 330 microg/ml lysozyme, 5 microg/ml DNAse and RNAse, freeze-thawed 3times in dry-ice/ethanol, centrifuged, adjusted to pH 7.4 and 8.0 with NaOH, incubated at 37°C or 50°C for 1 h
partial
recombinant enzyme from Escherichia coli by ion exchange chromatography and gel filtration
recombinant GST-tagged isoallelic forms K210 and E210 mutants from Escherichia coli to homogeneity
-
recombinant GST-tagged wild-type and mutant enzymes from Escherichia coli BL21 (DE3) by glutathione affinity chromatography, the GST-tag is cleaved off
-
recombinant GST-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) pLysS by glutathione affinity chromatgraphy, tag cleavage by thrombin, and ultrafiltration
-
recombinant His-tagged enzyme from Escherichia coli strain Rosetta (DE3) by nickel affinity chromatography, removal of the His-tag by thrombin and tag elimination by another step of nickel affinity chromatography
-
recombinant His-tagged enzyme from Escherichia coli, removal of the His-tag
-
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli BL21+; expression in Escherichia coli BL21+; expression in Escherichia coli BL21+
expression of wild-type and mutant enzymes in SH-SY5Y neuroblastoma cells, expression analysis
-
gene hemC, a single gene for PBGD in chromosome 5, recombinant expression of a codon-optimized PBGD gene in Escherichia coli
gene hemC, recombinant expression of His-tagged enzyme in Escherichia coli
-
gene hemC, recombinant expression of His-tagged enzyme in Escherichia coli strain Rosetta (DE3)
-
PBGD gene, DNA and amino acid sequence determination and analysis, expression of GST-tagged wild-type and mutant enzymes in Escherichia coli BL21 (DE3)
-
PCR-amplification, expression in Escherichia coli BL21Gold(DE3)(pLysS) with plasmid pET-14b(+)hemC
-
pTRE-EalAAT-hPBGD-WPRE plasmid from pTRE2 vector expressed in mice hepatocytes
recombinant expression of GST-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3) pLysS
-
the enzyme is expressed into a housekeeping or an erythroid form as a result of differential promoter usage and splicing, three pairs of isoallelic forms, expression of two of the isoallelic forms, K210 and E210, with mutations involved in acute intermittent porphyria, AIP, in Escherichia coli as GST fusion proteins
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
medicine
pharmacology
-
safety, pharmacokinetics and pharmacodynamics of recombinant human porphobilinogen deaminase P 9808, administered to healthy subjects and asymptomatic porphobilinogen deaminase-deficient subjects with high concentrations of porphobilinogen, the substrate of porphobilinogen deaminase for investigation and establishing of an alternative therapy of acute intermittent porphyria, AIP, overview
diagnostics
-
melting properties of mutant enzymes are used to diagnose acute intermittent porphyria in symptomatic and asymptomatic carriers with the high-resolution melting method
diagnostics
-
molecular analysis of the hydroxymethylbilane synthase confirms risk for acute intermittent porphyria
medicine
-
a HPLC method for simultaneous determination of porphobilinogen deaminase and uroporphobilinogen III synthase activity. The estimation of porphobilinogen deaminase activity is widely used for the diagnosis of acute intermittent porphyria where the abnormality of the enzyme is the primary genetic defect
medicine
-
acute intermittent porphyria is caused by partial deficiency of hydroxymethylbilane synthase affecting heme biosynthesis
medicine
cats with naturally occurring mutant enzymes can be used as animal model for acute intermittent porphyria; cats with naturally occurring mutant enzymes can be used as animal model for acute intermittent porphyria; cats with naturally occurring mutant enzymes can be used as animal model for acute intermittent porphyria
medicine
enzyme over-expression in hepatocytes reduces precursor accumulation, liver-directed gene therapy might offer an alternative to liver transplantation
medicine
enzyme over-expression in hepatocytes reduces precursor accumulation, liver-directed gene therapy might offer an alternative to liver transplantation
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wright, D.J.; Lim, C.K.
Simultaneous determination of hydroxymethylbilane synthase and uroporphyrinogen III synthase in erythrocytes by high-performance liquid chromatography
Biochem. J.
213
85-88
1983
Homo sapiens
brenda
Frydman, R.B.; Feinstein, G.
Studies on porphobilinogen deaminase and uroporphyrinogen III cosynthase from human erythrocytes
Biochim. Biophys. Acta
350
358-373
1974
Homo sapiens
brenda
Jordan, P.M.; Berry, A.
Preuroporphyrinogen, a universal intermediate in the biosynthesis of uroporphyrinogen III
FEBS Lett.
112
86-88
1980
Rhodobacter sphaeroides, Rhodobacter sphaeroides NCIB 8253
brenda
Levin, E.Y.; Coleman, D.L.
The enzymatic conversion of porphobilinogen to uroporphyrinogen catalyzed by extracts of hematopoietic mouse spleen
J. Biol. Chem.
242
4248-4253
1967
Mus musculus, Spinacia oleracea
-
brenda
Jordan, P.M.; Shemin, D.
Purification and properties of uroporphyrinogen I synthetase from Rhodopseudomonas spheroides
J. Biol. Chem.
248
1019-1024
1973
Rhodobacter sphaeroides
brenda
Davies, R.C.; Neuberger, A.
Polypyrroles formed from porphobilinogen and amines by uroporphyrinogen synthetase of Rhodopseudomonas spheroides
Biochem. J.
133
471-492
1973
Bos taurus, Glycine max, Rhodobacter sphaeroides, Rhodobacter sphaeroides NCIB 8253, Spinacia oleracea, Triticum aestivum
brenda
Miyagi, K.; Kaneshima, M.; Kawakami, J.; Nakada, F.; Petryka, Z.J.; Watson, C.J.
Uroporphyrinogen I synthetase from human erythrocytes: Separation, purification, and properties of isoenzymes
Proc. Natl. Acad. Sci. USA
76
6172-6176
1979
Bos taurus, Homo sapiens, Rhodobacter sphaeroides, Spinacia oleracea
brenda
Anderson, P.M.; Desnick, R.J.
Purification and properties of uroporphyrinogen I synthase from human erythrocytes
J. Biol. Chem.
255
1993-1999
1980
Homo sapiens
brenda
Battersby, A.R.; Fookes, C.J.R.; Matcham, G.W.J.; McDonald, E.
Biosynthesis of the pigments of life: formation of the macrocycle
Nature
285
17-19
1980
Euglena gracilis, Gallus gallus, Propionibacterium freudenreichii subsp. shermanii
brenda
Shioi, Y.; Nagamine, M.; Kuroki, M.; Sasa, T.
Purification by affinity chromatography and properties of uroporphyrinogen I synthetase from Chlorella regularis
Biochim. Biophys. Acta
616
300-309
1980
Chlorella regularis, Chlorella regularis S-50, Rhodobacter sphaeroides, Spinacia oleracea, Triticum aestivum
brenda
Russell, C.S.; Rockwell, P.
The effects of sulfhydryl reagents on the activity of wheat germ uroporphyrinogen I synthase
FEBS Lett.
116
199-202
1980
Triticum aestivum
brenda
Williams, D.C.; Morgan, G.S.; McDonald, E.; Battersby, A.R.
Purification of porphobilinogen deaminase from Euglena gracilis and studies of its kinetics
Biochem. J.
193
301-310
1981
Euglena gracilis
brenda
Williams, D.C.
Characterization of the multiple forms of hydroxymethylbilane synthase from rat spleen
Biochem. J.
217
675-683
1984
Rattus norvegicus
brenda
Farmer, D.J.; Hollebone, B.R.
Comparative inhibition of hepatic hydroxymethylbilane synthase by both hard and soft metal cations
Can. J. Biochem. Cell Biol.
62
49-54
1984
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
brenda
Brown, R.C.; Elder, G.H.; Urquhart, A.J.
Purification of hydroxymethylbilane synthase from human erythrocytes
Biochem. Soc. Trans.
13
1227-1228
1985
Homo sapiens
-
brenda
Helliwell, J.R.; Nieh, Y.P.; Raftery, J.; Cassata, A.; Habash, J.; Carr, P.D.; Ursby, T.; Wulff, M.; Thompson, A.W.; Niemann, A.C.; Haedener, A.
Time-resolved structures of hydroxymethylbilane synthase (Lys59Gln mutant) as it is loaded with substrate in the crystal determined by Laue diffraction
J. Chem. Soc. Faraday Trans.
94
2615-2622
1998
Escherichia coli
-
brenda
Hart, G.J.; Abell, C.; Battersby, A.R.
Purification, N-terminal amino acid sequence and properties of hydroxymethylbilane synthase (porphobilinogen deaminase) from Escherichia coli
Biochem. J.
240
273-276
1986
Escherichia coli
brenda
Mazzetti, M.B.; Tomio, J.M.
Purification and some properties of rat liver uroporphyrinogen I synthase
Anal. Asoc. Quim. Argent.
76
207-215
1988
Chlorella regularis, Escherichia coli, Homo sapiens, Rattus norvegicus, Spinacia oleracea
-
brenda
Miller, A.D.; Hart, G.J.; Packman, L.C.; Battersby, A.R.
Evidence that the pyrromethane cofactor of hydroxymethylbilane synthase (porphobilinogen deaminase) is bound to the protein through the sulphur atom of cysteine-242
Biochem. J.
254
915-918
1988
Escherichia coli, Escherichia coli TG1
brenda
Beifuss, U.; Hart, G.J.; Miller, A.D.; Battersby, A.R.
13C-N.M.R. Studies on the pyrromethane cofactor of hydroxymethylbilane synthase
Tetrahedron Lett.
29
2591-2594
1988
Escherichia coli
-
brenda
Smythe, E.; Williams, D.C.
A simple rapid purification scheme for hydroxymethylbilane synthase from human erythrocytes
Biochem. J.
251
237-241
1988
Homo sapiens
brenda
Lannfelt, L.; Wetterberg, L.; Lilius, L.; Thunell, S.; Joernvall, H.; Pavlu, B.; Wielburski, A.; Gellerfors, P.
Porphobilinogen deaminase in human erythrocytes
Scand. J. Clin. Lab. Invest.
49
677-684
1989
Homo sapiens
brenda
Sharif, A.; Smith, A.G.; Abell, C.
Isolation and characterisation of cDNA clone for chlorophyll synthesis enzyme from Euglena gracilis
Eur. J. Biochem.
184
353-359
1989
Escherichia coli, Euglena gracilis, Homo sapiens, Rattus norvegicus
brenda
Haedener, A.; Alefounder, P.; Hart, G.J.; Abell, C.; Battersby, A.R.
Investigation of putative active-site lysine residues in C
Biochem. J.
271
487-491
1990
Escherichia coli
brenda
Corrigall, A.V.; Meissner, P.N.; Kirsch, R.E.
Purification of human erythrocyte porphobilinogen deaminase
S. Afr. Med. J.
80
294-269
1991
Homo sapiens
brenda
Spano, A.J.; Timko, M.P.
Isolation, characterization and partial amino acid sequence of a chloroplast-localized porphobilinogen deaminase from pea (Pisum sativum L.)
Biochim. Biophys. Acta
1076
29-36
1991
Glycine max, Pisum sativum
brenda
Jordan, P.M; Warren, M.J.; Mgbeje, B.I.A.; Wood, S.P.; Cooper, J.B.; Louie, G.; Brownlie, P.; Lambert, R.; Blundell, T.L.
Crystallization and preliminary X-ray investigation of Escherichia coli porphobilinogen deaminase.
J. Mol. Biol.
224
269-271
1992
Escherichia coli
brenda
Meissner, P.; Adams, P.; Kirsch, R.
Allosteric inhibition of human lymphoblast and purified porphobilinogen deaminase by protoporphyrinogen and coproporphyrinogen
J. Clin. Invest.
91
1436-1444
1993
Homo sapiens
brenda
Haedener, A.; Matzinger, P.K.; Malashkevich, V.N.; Louie, G.V.; Wood, S.P.; Oliver, P.; Alefounder, P.R.; Pitt, A.R.; Abell, C.; Battersby, A.R.
Purification, characterization, crystallisation and X-ray analysis of selenomethionine-labelled hydroxymethylbilane synthase from Escherichia coli
Eur. J. Biochem.
211
615-624
1993
Escherichia coli
brenda
Araujo, L.S.; Lombardo, M.E.; Batlle, A.M.D.C.
Inhibition of porphobilinogenase by porphyrins in Saccharomyces cerevisiae
Int. J. Biochem.
26
1377-1381
1994
Saccharomyces cerevisiae
brenda
Juknat, A.A.; Doernemann, D.; Senger, H.
Purification and kinetic studies on a porphobilinogen deaminase from the unicellular green alga Scenedesmus obliquus
Planta
193
123-130
1994
Chlorella regularis, Escherichia coli, Euglena gracilis, Homo sapiens, Pisum sativum, Rattus norvegicus, Rhodobacter sphaeroides, Saccharomyces cerevisiae, Spinacia oleracea, Tetradesmus obliquus
-
brenda
Jones, R.M.; Jordan, P.M.
Purification and properties of porphobilinogen deaminase from Arabidopsis thaliana
Biochem. J.
299
895-902
1994
Arabidopsis thaliana
-
brenda
Cardalda, C.A.; Juknat, A.A.; Princ, F.G.; Batlle, A.
Rat harderian gland porphobilinogen deaminase: characterization studies and regulatory action of protoporphyrin IX
Arch. Biochem. Biophys.
347
69-77
1997
Rattus norvegicus
brenda
Shoolingin-Jordan, P.M.; Al-Dbass, A.; McNeill, L.A.; Sarwar, M.; Butler, D.
Human porphobilinogen deaminase mutations in the investigation of the mechanism of dipyrromethane cofactor assembly and tetrapyrrole formation
Biochem. Soc. Trans.
31
731-735
2003
Homo sapiens
brenda
Schneider-Yin, X.; Hergersberg, M.; Schuurmans, M.M.; Gregor, A.; Minder, E.I.
Mutation hotspots in the human porphobilinogen deaminase gene: recurrent mutations G111R and R173Q occurring at CpG motifs
J. Inherit. Metab. Dis.
27
625-631
2004
Homo sapiens
brenda
Gruenberg-Etkovitz, N.; Greenbaum, L.; Grinblat, B.; Malik, Z.
Proteasomal degradation regulates expression of porphobilinogen deaminase (PBGD) mutants of acute intermittent porphyria
Biochim. Biophys. Acta
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2006
Homo sapiens
brenda
Sardh, E.; Rejkjaer, L.; Andersson, D.E.; Harper, P.
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Homo sapiens
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Poblete-Gutierrez, P.; Wiederholt, T.; Martinez-Mir, A.; Merk, H.F.; Connor, J.M.; Christiano, A.M.; Frank, J.
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Homo sapiens (P08397)
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Ulbrichova, D.; Flachsova, E.; Hrdinka, M.; Saligova, J.; Bazar, J.; Raman, C.S.; Martasek, P.
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Homo sapiens
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Brons-Poulsen, J.; Christiansen, L.; Petersen, N.E.; Horder, M.; Kristiansen, K.
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Homo sapiens
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Homo sapiens, Homo sapiens (P08397)
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Homo sapiens
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Li, N.; Chu, X.; Wu, L.; Liu, X.; Li, D.
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Rattus norvegicus (P19356)
brenda