Information on EC 4.2.1.24 - porphobilinogen synthase

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

EC NUMBER
COMMENTARY hide
4.2.1.24
-
RECOMMENDED NAME
GeneOntology No.
porphobilinogen synthase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
2 5-aminolevulinate = porphobilinogen + 2 H2O
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
condensation
-
-
elimination
-
-
of H2O, C-O bond clevage
-
Knorr reaction
-
Knorr pyrrole synthesis, C-C bond formation
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
-
-
heme metabolism
-
-
Metabolic pathways
-
-
Porphyrin and chlorophyll metabolism
-
-
tetrapyrrole biosynthesis I (from glutamate)
-
-
tetrapyrrole biosynthesis II (from glycine)
-
-
SYSTEMATIC NAME
IUBMB Comments
5-aminolevulinate hydro-lyase (adding 5-aminolevulinate and cyclizing; porphobilinogen-forming)
The enzyme catalyses the asymmetric condensation and cyclization of two 5-aminolevulinate molecules, which is the first common step in the biosynthesis of tetrapyrrole pigments such as porphyrin, chlorophyll, vitamin B12, siroheme, phycobilin, and cofactor F430. The enzyme is widespread, being essential in organisms that carry out respiration, photosynthesis, or methanogenesis. The enzymes from most organisms utilize metal ions (Zn2+, Mg2+, K+, and Na+) as cofactors that reside at multiple sites, including the active site and allosteric sites. Enzymes from archaea, yeast, and metazoa (including human) contain Zn2+ at the active site. In humans, the enzyme is a primary target for the environmental toxin Pb. The enzymes from some organisms utilize a dynamic equilibrium between architecturally distinct multimeric assemblies as a means for allosteric regulation.
CAS REGISTRY NUMBER
COMMENTARY hide
9036-37-7
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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-
-
Manually annotated by BRENDA team
mutant strain C-2A'
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Archaeoglobus sp.
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
Candida sp.
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Chlamydomonas sp.
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Escherichia coli Rosetta(DE3)
Rosetta(DE3)
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Methanococcus sp.
-
-
-
Manually annotated by BRENDA team
Methanothermus sp.
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Physcomitrella sp.
-
-
-
Manually annotated by BRENDA team
the Plasmodium falciparum enzyme may account for about 10% of the total delta-aminolevulinate dehydratase activity in the parasite, the rest being accounted for by the host enzyme imported by the parasite
-
-
Manually annotated by BRENDA team
Propionibacterium sp.
-
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
SpragueDawley
-
-
Manually annotated by BRENDA team
animals infected with Trypanosoma evansi
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Schizosaccharomyces sp.
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
ATCC 25520
-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
5-aminolevulinate
?
show the reaction diagram
5-aminolevulinate
porphobilinogen + H2O
show the reaction diagram
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
5-aminolevulinic acid + 5-aminolevulinic acid
porphobilinogen + 2 H2O
show the reaction diagram
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
2 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
5-aminolevulinate
?
show the reaction diagram
5-aminolevulinate
porphobilinogen + H2O
show the reaction diagram
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
about 80% reactivation of the demetalled protein
Cu2+
-
inhibits enzymatic activity. High molecular weight fraction as well as metallothionein are involved in the detoxification of harmful heavy metals
Li+
-
stimulates
Na+
-
stimulates
Ni(2+)
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(4E)-6-oxodec-4-enedioic acid
-
-
1,1',1''-[(3-ethoxyprop-1-ene-1,1,2-triyl)triselanyl]tribenzene ethyl 2,3,3-tris(phenylselanyl)prop-2-en-1-yl ether
-
0.6 mM, 65% inhibition
1,1',1''-[(3-ethoxyprop-1-ene-1,1,2-triyl)triselanyl]tris(2,4,6-trimethylbenzene) ethyl 2,3,3-tris[(2,4,6-trimethylphenyl)selanyl]prop-2-en-1-yl ether
-
0.6 mM, 44% inhibition
1,1',1''-[(3-ethoxyprop-1-ene-1,1,2-triyl)triselanyl]tris(4-chlorobenzene) ethyl 2,3,3-tris[(4-chlorophenyl)selanyl]prop-2-en-1-yl ether
-
modest inhibition
1,10-phenanthroline
1-amino-4-hydroxy-2-butanone
-
-
1-amino-4-methoxy-2-butanone
-
-
1-amino-5-hydroxy-2-pentanone
-
-
2,2'-dipyridine
-
-
2,2-difluorosuccinic acid
-
competitive
2,3-dimercaptopropane-1-sulfonic acid
2,3-Dimercaptopropanol
-
cysteine and ZnCl2 protects. Dithiothreitol protects inhibition by 1 mM 2,3-dimercaptopropanol in a concentration dependent manner
2-bromo-3-(imidazol-5-yl)propionic acid
-
-
3-acetyl-4-oxoheptane-1,7-dioic acid
-
formation of a Schiff base complex between the inhibitors and the active site Lys
-
4,7-dioxosebacic acid
-
hanging-drop method, irreversible inhibitor binds by forming Schiff-base linkages with lysines 200 and 253 at the active site. 4,7-dioxosebacic acid is a better inhibitor of the zinc-dependent 5-aminolaevulinic acid dehydratases than of the zinc-independent 5-aminolaevulinic acid dehydratases
4,7-dioxosebaic acid
-
-
4-amino-3-oxobutanoate
-
-
4-nitro-2-butanone
-
-
4-oxo-pentanenitrile
-
-
4-oxo-sebacic acid
-
-
4-oxosebaic acid
-
active site-directed irreversible inhibitor, less potent than 4,7-dioxosebaic acid
5,5'-dithio(bis-2-nitrobenzoic acid)
-
-
5,5'-dithiobis(2-nitrobenzoic acid)
-
-
5,5'-iminobis(4-oxopentanoic acid)
-
-
5,5'-oxybis(4-oxopentanoic acid)
-
-
5,5'-sulfinylbis(4-oxopentanoic acid)
-
-
5,5'-sulfonylbis(4-oxopentanoic acid)
-
-
5,5'-thiobis(4-oxopentanoic acid)
-
-
5-amino-4-oxopentanenitrile
-
-
5-bromo-levulinic acid
-
-
5-bromolevulinic acid
-
-
-
5-chlorolevulinic acid
5-fluorolevulinic acid
-
both inhibitor molecules are covalently bound to two conserved, active-site lysine residues, Lys205 and lys260, through Schiff bases
5-hydroxy-4-oxo-L-norvaline
-
competitive
5-hydroxy-4-oxopentanoic acid
-
-
5-hydroxylaevulinic acid
-
the competitive inhibitor is bound by a Schiff-base link to one of the invariant active-site lysine residues (Lys263). The inhibitor appears to bind in two well defined conformations
5-hydroxylevulinate
-
competitive
-
5-hydroxylevulinic acid
-
-
5-iodolevulinic acid
-
-
-
5-nitrilo-4-oxopentanoic acid
-
-
-
5-oxo-hexanoic acid
-
-
6-amino-5-oxohexanoic acid
-
-
7-(3-aminopentan-3-yl)-5-chloroquinolin-8-ol
-
using in silico screening two hexamer-stabilizing inhibitors of PBGS are identified: N-(3-methoxyphenyl)-1-methyl-6-oxo-2-[(pyridin-2-ylmethyl)sulfanyl]-1,6-dihydropyrimidine-5-carboxamide and 7-(3-aminopentan-3-yl)-5-chloroquinolin-8-ol
8-hydroxyquinoline
-
-
8-Hydroxyquinoline-5-sulfonic acid
-
-
Al2(SO4)3
-
ALA-D inhibition may be due to the fact that aluminum present in the growth medium can compete with Mg2+ or reduce the expression of ALA-D
Al3+
-
IC50: 0.319 mM, GSH has no protective effect
alaremycin
-
porphobilinogen synthase is cocrystallized with the alaremycin. At 1.75 A resolution, the crystal structure reveals that the antibiotic efficiently blocks the active site of porphobilinogen synthase. The antibiotic binds as a reduced derivative of 5-acetamido-4-oxo-5-hexenoic acid. The corresponding methyl group is not coordinated by any amino acid residues of the active site, excluding its functional relevance for alaremycin inhibition. Alaremycin is covalently bound by the catalytically important active-site lysine residue 260 and is tightly coordinated by several active-site amino acids
AlCl3
-
0.001-0.01 mM AlCl3
alloxan
-
i.e. 2,4,5,6-tetraoxypyrimidine 5,6-dioxyuracil , 0.00125-0.02 mM alloxan causes a concentration-dependent uncompetitive inhibition. Dithiothreitol (0.7and 1 mM) completely prevents the inhibition induced by 0.01 and 0.02 mM alloxan. Similar protection is obtained in the presence of 2 mMglutathione
alpha-lipoic acid
-
significant inhibition
arsenic acid
-
inhibition of 5-aminolevulinic acid dehydratase activity by arsenic in excised etiolated maize leaf segments during greening. KNO3, chloramphenical, cycloheximide, DTNB and levulinic aciddecrease inhibition. GSH increase inhibition
ascorbic acid
-
0.4 mM, 23% inhibition
bathocuproine disulfonic acid
bis(4-chlorophenyl)diselenide
-
-
-
bis(4-methoxyphenyl)diselenide
-
-
-
bis[3-(trifluoromethy)phenyl]diselenide
-
-
-
Butanedione
-
protection by 5-aminolevulinate
Carbonate
-
using a carbonate buffer rather than phosphate causes nearly a 90% drop in activity in the developed assay method
Coproporphyrinogen III
-
-
Cuprizone
-
bis-cyclohexanoneoxaldihydrazone
D-fructose
-
formation of a Schiff base with the critical lysine residue of the enzyme is involved in inhibition of the enzyme by hexoses and pentoses
D-glucose
D-ribose
-
formation of a Schiff base with the critical lysine residue of the enzyme is involved in inhibition of the enzyme by hexoses and pentoses
D-xylose
-
-
diammine(dichloro)platinum
-
mechanism of inhibition is a direct interaction of the inhibitor with sulfhydryl groups, whereas zinc site appears to be involved with the higher doses only
dibutyl diselenide
dicholesteroyl diselenide
-
significant at 0.1 mM
diethyl dicarbonate
-
-
diethyldithiocarbamate
-
-
diphenyl diselenide
diphenyl ditelluride
-
dithiothreitol protects
DTNB
-
reversible loss of activity
ebselen
-
dithiothreitol protects
Fe2+
-
noncompetitive
Ga3+
-
inhibits by competing with Zn2+, IC50: 0.442 mM, GSH has no protective effect, Zn2+ completely recovers inhibition
GSH
-
a weak inhibitor
HgCl2
-
pretreatment with a nontoxic dose of Na2SeO3 partially or totally prevents in vivo mercury effects in kidney, including prevention of inhibition of delta-aminolevulinate dehydratase
In3+
-
inhibits by competing with Zn2+, IC50: 0.298 mM, GSH reduces inhibition, DL-dithiothreitol has modest effect on inhibition, Zn2+ completely recovers inhibition
-
iodoacetamide
iodoacetate
K2SO4
-
slight
levulinic acid
Mercury ions
-
-
-
meso-2,3-dimercaptosuccinic acid
methyl methanethiosulfonate
-
-
N-(3-methoxyphenyl)-1-methyl-6-oxo-2-[(pyridin-2-ylmethyl)sulfanyl]-1,6-dihydropyrimidine-5-carboxamide
-
using in silico screening two hexamer-stabilizing inhibitors of PBGS are identified: N-(3-methoxyphenyl)-1-methyl-6-oxo-2-[(pyridin-2-ylmethyl)sulfanyl]-1,6-dihydropyrimidine-5-carboxamide and 7-(3-aminopentan-3-yl)-5-chloroquinolin-8-ol
Na2SeO3
-
inhibits renal and hepatic enzyme
Neocuproine
-
2,9-dimethyl-1,10-phenanthroline
Ni2+
-
0.5 mM, 8% inhibition
p-hydroxymercuribenzoate
-
-
phenyl selenoacetylene
phenyl selenoxideacetylene
phosphate
-
competitive against Mg2+
protoporphyrin IX
-
-
pyridoxal 5'-phosphate
pyridoxal phosphate
-
-
pyridoxamine phosphate
-
-
rac-2-hydroxy-4-oxopentanoic acid
-
-
-
rac-3-hydroxy-4-oxopentanoic acid
-
-
-
sodium selenide
succinic acid
-
noncompetitive
succinic acid monomethyl ester
-
competitive
succinylacetone
Tl3+
-
inhibits by direct oxidation of essential sulfhydryl groups, IC50: 0.0085 mM, DL-dithiothreitol restores completely enzyme activity inhibited by Tl3+, Zn2+ is unable to change inhibition
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
-
required at very low concentrations of substrate
glucose
-
incubations of erythrocytes for 24 h with glucose result in an increase of delta-ALA-D activity. Incubations of erythrocytes with 100 to 200 mM glucose for 48 h inhibit delta-ALA-D activity
NH4+
-
stimulates
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.043 - 2
5-aminolevulinate
0.00032 - 18
5-aminolevulinic acid
additional information
additional information
-
the kinetic data do not follow a simple Michaelis-Menten relationship, but can be attributed to catalysis by two different forms of the enzyme that have different Km-values
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
16.1
5-aminolevulinic acid
Pseudomonas aeruginosa
-
-
additional information
additional information
Homo sapiens
-
-
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
50300
5-aminolevulinic acid
Pseudomonas aeruginosa
-
-
4489
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
26.52
1-amino-4-hydroxy-2-butanone
-
-
7
2,2-difluorosuccinic acid
-
-
73.04
4-oxo-pentanenitrile
-
-
2.93
4-oxo-sebacic acid
-
-
0.2 - 0.313
5,5'-iminobis(4-oxopentanoic acid)
0.098 - 0.963
5,5'-oxybis(4-oxopentanoic acid)
9.94 - 10.8
5,5'-sulfinylbis(4-oxopentanoic acid)
0.342 - 11
5,5'-sulfonylbis(4-oxopentanoic acid)
0.06 - 38.4
5,5'-thiobis(4-oxopentanoic acid)
18.48
5-amino-4-oxopentanenitrile
-
-
4.05
5-hydroxylevulinic acid
-
37C, pH 8.5
3.05
5-oxo-hexanoic acid
-
-
1.07
6-amino-5-oxohexanoic acid
-
-
1.33
alaremycin
-
-
0.00364
alloxan
-
pH 6.4 and 37C
0.03
diethyl dicarbonate
-
-
0.96 - 1.5
levulinic acid
0.0025
protoporphyrin IX
-
-
0.03
pyridoxal phosphate
-
-
9
succinic acid
-
-
1.9
succinic acid monomethyl ester
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
30
1-amino-4-methoxy-2-butanone
Rattus sp.
-
-
32.5
1-amino-5-hydroxy-2-pentanone
Rattus sp.
-
-
0.31
5,5'-iminobis(4-oxopentanoic acid)
Pseudomonas aeruginosa
-
-
0.96
5,5'-oxybis(4-oxopentanoic acid)
Pseudomonas aeruginosa
-
-
38
5,5'-sulfinylbis(4-oxopentanoic acid)
Pseudomonas aeruginosa
-
-
9.9
5,5'-sulfonylbis(4-oxopentanoic acid)
Pseudomonas aeruginosa
-
-
0.34
5,5'-thiobis(4-oxopentanoic acid)
Pseudomonas aeruginosa
-
-
0.01
7-(3-aminopentan-3-yl)-5-chloroquinolin-8-ol
Homo sapiens
-
-
0.319
Al3+
Bos taurus
-
IC50: 0.319 mM, GSH has no protective effect
1.33
alaremycin
Pseudomonas aeruginosa
-
-
0.004
alloxan
Mus musculus
-
pH 6.4 and 37C
0.01917 - 0.0345
Cd2+
0.01 - 0.985
dibutyl diselenide
0.00195 - 0.274
diphenyl diselenide
0.442
Ga3+
Bos taurus
-
inhibits by competing with Zn2+, IC50: 0.442 mM, GSH has no protective effect, Zn2+ completely recovers inhibition
0.298
In3+
Bos taurus
-
inhibits by competing with Zn2+, IC50: 0.298 mM, GSH reduces inhibition, DL-dithiothreitol has modest effect on inhibition, Zn2+ completely recovers inhibition
-
0.058
N-(3-methoxyphenyl)-1-methyl-6-oxo-2-[(pyridin-2-ylmethyl)sulfanyl]-1,6-dihydropyrimidine-5-carboxamide
Homo sapiens
-
-
0.0056 - 0.0062
Pb2+
0.25 - 0.4
phenyl selenoacetylene
0.045 - 0.1
phenyl selenoxideacetylene
0.005 - 0.902
sodium selenide
0.001
succinylacetone
Toxoplasma gondii
-
-
0.0085
Tl3+
Bos taurus
-
inhibits by direct oxidation of essential sulfhydryl groups, IC50: 0.0085 mM, DL-dithiothreitol restores completely enzyme activity inhibited by Tl3+, Zn2+ is unable to change inhibition
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.09
-
expressed from expression vector pLM1
0.28
-
expressed from expression vector pET28a+
0.29
-
expressed from expression vector pET28a+, His-tag removed
0.31
-
-
0.63
-
-
0.67
-
wild-type octamer
6.98
-
shell gland enzyme
10.3
-
liver enzyme
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.9 - 8
-
pH 5.9: about 50% of maximal activity, pH 8.0: about 70% of maximal activity, wild-type enzyme
6.3 - 6.4
-
-
6.3
-
-
6.3 - 6.7
-
-
6.9 - 7.1
-
-
7.5 - 8
-
-
7.5 - 8.5
-
-
7.7 - 9.2
-
-
8 - 8.6
-
in citrate buffer, Tris-maleate buffer, imidazole buffer and Tris buffer
8.6
-
in presence of Mg2+ and K+
9.4
-
two pH-optima at pH 8.5 and at pH 9.4
additional information
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 9
-
pH 6.0: about 70% of maximal activity, pH 9.0: about 55% of maximal activity
6.5 - 9.5
-
pH 6.5: about 80% of maximal activity, pH 9.5: about 45% of maximal activity
7 - 10
-
pH 7.0: about 50% of maximal activity, pH 10.0: about 55% of maximal activity
7.5 - 9.8
-
pH 7.5: about 35% of maximal activity, pH 9.8: about 50% of maximal activity
7.6 - 8
-
enzyme activity is not inhibited when the pH is between 7.6 and 8.0, and enzyme activity is only inhibited by 1.3% at pH 8.2
7.8 - 8
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25 - 45
-
25C: about 75% of maximal activity, 45C: about 85% of maximal activity
37 - 75
-
37C: about 30% of maximal activity, 75C: about 90% of maximal activity
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.4
-
isoelectric focusing, pH-range 3-10
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
Friend erythroleukemia cell line 586
Manually annotated by BRENDA team
-
maximal activity before pigmentation of the egg shell
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
Chlorobaculum parvum (strain NCIB 8327)
Chlorobaculum parvum (strain NCIB 8327)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
32000
-
subunit of L273R, analyzed by SDS-PAGE
34800
-
analyzed by SDS-PAGE
36000
-
subunit, analyzed by SDS-PAGE
36690
-
theoretical monomer molecular mass
69600
-
mutant enzyme W19A, pH 7, analytical ultracentrifugation
78600
-
mutant enzyme W19A, pH 7, dynamic light scattering
183500
-
mutant enzyme R240A, pH 9, analytical ultracentrifugation
188500
-
mutant enzyme R240A, pH 7, analytical ultracentrifugation
197000
-
variant F12L, equilibrium sedimentation
197900
-
mutant enzyme F12L, pH 7, analytical ultracentrifugation
212400
-
mutant enzyme R240A, pH 7, dynamic light scattering
214400
-
mutant enzyme F12L, pH 7, dynamic light scattering
220000
gel filtration, analytical ultracentrifugation
240000
-
gel filtration
244000
252000
-
gel filtration
260000
270000
-
gel filtration
275000
-
glycerol density gradient centrifugation
280000
282000
285000
-
gel filtration
289000
-
equilibrium sedimentation
309000
-
gel filtration
317600
-
wild-type enzyme, pH 7, dynamic light scattering
320000
-
gel filtration, recombinant TgPBGS is purified as a stable octamer
324000
-
density gradient centrifugation
335000
-
gel filtration
345000
-
gel filtration
350000
-
gel filtration
additional information
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hexamer
hexamer or octamer
-
by analytical ultracentrifugation
octamer
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal structure of enzyme complexed with 4-oxosebaic acid and of enzyme complexed with 4,7-dioxosebaic acid
-
X-ray structure of the enzyme complexed with the inhibitor levulinic acid at 2.0 A resolution
-
sitting-drop vapour-diffusion method
-
hanging drop method, enzyme complexed with the inhibitor laevulinic acid at 2.6 A resolution, unit cell parameters: a = 125.24 A, b = 125.24 A, c = 164.6 A and spec group P42(1)2
-
hanging drop vapor-diffusion method. Crystal structures of the active site of Pseudomonas aeruginosa PBGS with the various inhibitors 5-hydroxylevulinic acid, 5,5'-oxybis(4-oxopentanoic acid), 5,5'-iminobis(4-oxopentanoic acid), 5,5'-thiobis(4-oxopentanoic acid), 5,5'-sulfinylbis(4-oxopentanoic acid) or 5,5'-sulfonylbis(4-oxopentanoic acid)
-
hanging drop vapour diffusion method, crystals of the enzyme complex with levulinic acid solved at 1.67 A resolution, crystals belong to space group P42(1)2 with cell dimensions of a = b = 129.8 A, c = 86.7 A
-
porphobilinogen synthase is cocrystallized with the alaremycin
-
structure of the active-site variant D139N of the Mg2+-dependent enzyme in complex with the inhibitor 5-fluorolevulinic acid
-
hanging-drop vapour diffusion method, X-ray structure of the enzyme in which the catalytic site of the enzyme is complexed with a putative cyclic intermediate composed of both substrate moieties, solved at 0.16 nm resolution
-
the X-ray structure of the enzyme complexed with the competitive inhibitor 5-hydroxylaevulinic acid, determined at a 1.9 A resolution
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
9
-
highest stability at
210720
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
55
-
90 min, 50% inactivation
60
-
30 min, 50% inactivation
64
-
60 min, 20% loss of activity
80
-
15 min, 50% loss of activity
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
EGTA prevents proteolysis
-
immobilized enzyme, continous operation for 9 days at 31 C, at a flow rate of 30 ml/h little loss of activity
-
Mg2+ stabilizes the quarternary structure of the protein
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
sensitive to oxygen, t1/2: 135 min, the oxygen-inactivated enzyme is restored to full activity by incubation with thiols
-
210688
total but reversible loss of activity by O2
-
210686
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, protein concentration above 2 mg/ml, 20 mM phosphate, 5 mM dithiothreitol, pH 6.8, stable for 6 months
-
-80C, one year
-
4C, one week, without significant change of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
apparent homogeneity (analyzed by SDS-PAGE)
-
native enzyme by ammonium sulfate fractionation, anion exchange chromatography, and gel filtration
-
two-step purification
-
using affinity chromatography and anion-exchange chromatography
-
using Ni-NTA chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli as a His-tagged fusion protein
-
expression in Escherichia coli
hexa-His-tag, removed by cleavage with thrombin
-
His-tagged
-
recombinant TgPBGS is expressed in Escherichia coli as a His-tagged fusion protein
-
structure of 5-aminolaevulinic acid dehydratase complexed with the irreversible inhibitor 4,7-dioxosebacic acid
-
very poor expression of full-length cDNA, overexpression of cDNA-2 (56 to 451 aa) as a protein with a histidine tag or as a GST fusion protein in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
liver and kidney enzyme activity presents a significant decrease in the diabetic/saline group when compared to the control/saline group
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H10F
-
mutant enzyme is active but is not inhibited by zinc. H10F binds a catalytic zinc at 0.5/subunit and binds a second nonessential and noninhibitory zinc at 0.5/subunit
K195A
-
mutant enzyme with only 0.1% of the wild-type activity
K195C
-
mutant enzyme with only 0.1% of the wild-type activity, 2-bromethylamine results in recovery of 10% of the wild-type activity
K247A
-
inactive mutant enzyme
K247C
-
inactive mutant enzyme, 2-bromethylamine results in recovery of 6% of the wild-type activity
A274K
-
naturally occurring ALAD porphyria-associated human PBGS mutants are shown to have an increased susceptibility to inhibition by both N-(3-methoxyphenyl)-1-methyl-6-oxo-2-[(pyridin-2-ylmethyl)sulfanyl]-1,6-dihydropyrimidine-5-carboxamide and 7-(3-aminopentan-3-yl)-5-chloroquinolin-8-ol
C132R
-
enzyme activity undetectable
G133R
-
11% of wild-type activity
K59N
-
112% of wild-type activity
K59N/G133R
-
22% of wild-type activity
L273R
-
enzyme activity undetectable
R221K
-
mutation in wild-type or chimeric enzymes reduces activity
R240A
-
mutant enzyme assembles into a metastable hexamer, which can undergo a reversible conversion to the octamer in the presence of substrate
R240AS
-
metastable nature of the R240A hexamer
V153M
-
about 67% of wild-type activity
W19A
-
assembles into a mixture of stable dimers
C326A
-
no effect on enzymatic activity
DELTA646-658
-
a mutant enzyme lacking the C-terminal 13 amino acids distinguishing parasite PBGS from plant and animal enzymes is purified as a dimer, suggesting that the C-terminus is required for octamer stabilisation
additional information
-
chimeric proteins that contain the aspartate-rich sequences of the pea enzyme or the enzyme from Pseudomonas aeruginosa in place of the naturally occuring cysteine-rich sequence of the human enzyme. The chimeric enzymes are substantially activated by both magnesium and potassium, but not by zinc. The specific activities of the chimeras are significantly lower than the specific activity of the wild-type enzyme
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
diagnostics
environmental protection
-
the enzyme can be used as a biomarker for Pb2+ contamination
medicine
-
delta-ALA-D activity is a reliable marker for oxidative stress in bone marrow transplantation patients