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4.2.1.24: porphobilinogen synthase

This is an abbreviated version!
For detailed information about porphobilinogen synthase, go to the full flat file.

Word Map on EC 4.2.1.24

Reaction

2 5-aminolevulinate =

porphobilinogen
+ 2 H2O

Synonyms

5-aminolaevulinic acid dehydratase, 5-aminolevulinate dehydrase, 5-aminolevulinate dehydratase, 5-aminolevulinate hydro-lyase (adding 5-aminolevulinate and cyclizing), 5-aminolevulinic acid dehydrase, 5-aminolevulinic acid dehydratase, 5-levulinic acid dehydratase, Al-D, ALA dehydratase, ALA synthetase, ALA-D, ALAD, ALADH, aminolevulinate dehydrase, aminolevulinate dehydratase, aminolevulinic dehydratase, CF-2, d-ALAD, delta aminolevulinic acid dehydratase, delta-ALA-D, delta-ALAD, delta-aminolevulinate dehydrase, delta-aminolevulinate dehydratase, delta-aminolevulinate dehydrataseALAD, delta-aminolevulinic acid dehydrase, delta-aminolevulinic acid dehydratase, delta-aminolevulinic dehydratase, gamma-aminolevulinic acid dehydratase, HemB, PaPBGS, PBG synthase, PBG-S, PBG-synthase, PBGS, Pcal_1709, PfALAD, PGBS, Porphobilinogen synthase, porphobilinogen synthetase, synthase, porphobilinogen, TgPBGS

ECTree

     4 Lyases
         4.2 Carbon-oxygen lyases
             4.2.1 Hydro-lyases
                4.2.1.24 porphobilinogen synthase

Inhibitors

Inhibitors on EC 4.2.1.24 - porphobilinogen synthase

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INHIBITOR
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-(trifluoromethyl)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
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
-
-
protoporphyrinogen IX
-
feedback inhibition by downstream intermediate
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
-