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
4.2.1.24
-
RECOMMENDED NAME
GeneOntology No.
porphobilinogen synthase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
2 5-aminolevulinate = porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
2 5-aminolevulinate = porphobilinogen + 2 H2O
show the reaction diagram
requires an active Arg residue and the formation of a Schiff base between the enzyme and 5-aminolevulinate
-
2 5-aminolevulinate = porphobilinogen + 2 H2O
show the reaction diagram
substrate is covalently bound through a Schiff base
-
2 5-aminolevulinate = porphobilinogen + 2 H2O
show the reaction diagram
substrate is covalently bound through a Schiff base
-
2 5-aminolevulinate = porphobilinogen + 2 H2O
show the reaction diagram
mechanism
-
2 5-aminolevulinate = porphobilinogen + 2 H2O
show the reaction diagram
catalytic mechanism in which the C-C bond linking both substrates in the intermediate is formed before the C-N bond
-
2 5-aminolevulinate = porphobilinogen + 2 H2O
show the reaction diagram
catalytic mechanism initiated by a C-C bond formation between A and P-side 5-aminolevulinic acid, followed by the formation of the intersubstrate Schiff base yielding the product porphobilinogen
-
2 5-aminolevulinate = porphobilinogen + 2 H2O
show the reaction diagram
reaction mechanism involving asymmetric addition and cyclization of two 5-aminolevulinate molecules, modeling, detailed overview. The active site consists of several invariant residues, including two lysyl residues Lys210 and Lys263 that bind the two substrate moieties as Schiff bases, active site structure and substrate binding, overview. The intersubstrate C-N bond is formed first have a rate-limiting barrier that is lower than those in which the intersubstrate C-C bond is formed first
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
condensation
-
-
elimination
-
-
of H2O, C-O bond clevage
-
Knorr reaction
-
Knorr pyrrole synthesis, C-C bond formation
PATHWAY
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
-
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.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5-aminolaevulinic acid dehydratase
-
-
5-aminolevulinate dehydrase
-
-
-
-
5-aminolevulinate dehydratase
-
-
-
-
5-aminolevulinate dehydratase
-
-
5-aminolevulinate dehydratase
-
-
5-aminolevulinate dehydratase
Escherichia coli Rosetta(DE3)
-
-
-
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
-
-
ALAD
-
-
-
-
ALAD
-
-
ALAD
-
-
ALAD
-
-
ALADH
-
-
-
-
aminolevulinate dehydrase
-
-
-
-
aminolevulinate dehydratase
-
-
-
-
aminolevulinic dehydratase
-
-
-
-
CF-2
-
240-kDa proteasome inhibitor
d-ALAD
-
-
delta-ALA-D
-
-
delta-ALA-D
Rattus norvegicus Wistar
-
-
-
delta-ALAD
-
-
-
-
delta-aminolevulinate dehydrase
-
-
-
-
delta-aminolevulinate dehydratase
-
-
-
-
delta-aminolevulinate dehydratase
-
-
delta-aminolevulinate dehydratase
-
-
delta-aminolevulinate dehydratase
Rattus norvegicus Wistar
-
-
-
delta-aminolevulinic acid dehydrase
-
-
-
-
delta-aminolevulinic acid dehydratase
-
-
-
-
delta-aminolevulinic acid dehydratase
-
-
delta-aminolevulinic acid dehydratase
-
-
delta-aminolevulinic acid dehydratase
-
-
delta-aminolevulinic acid dehydratase
-
-
delta-aminolevulinic acid dehydratase
-
-
delta-aminolevulinic acid dehydratase
-
-
delta-aminolevulinic dehydratase
-
-
-
-
delta-aminolevulinic dehydratase
-
-
gamma-aminolevulinic acid dehydratase
-
-
-
-
PBG synthase
-
-
PBG-synthase
-
-
PBG-synthase
Rattus norvegicus Wistar
-
-
-
PBGS
-
-
Porphobilinogen synthase
-
-
-
-
Porphobilinogen synthase
-
-
Porphobilinogen synthase
-
-
Porphobilinogen synthase
-
-
Porphobilinogen synthase
-
-
Porphobilinogen synthase
-
-
Porphobilinogen synthase
-
-
porphobilinogen synthetase
-
-
-
-
synthase, porphobilinogen
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9036-37-7
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
Archaeoglobus sp.
-
-
-
Manually annotated by BRENDA team
Candida sp.
-
-
-
Manually annotated by BRENDA team
Chlamydomonas sp.
-
-
-
Manually annotated by BRENDA team
Rosetta(DE3)
-
-
Manually annotated by BRENDA team
Escherichia coli Rosetta(DE3)
Rosetta(DE3)
-
-
Manually annotated by BRENDA team
workers occupationally exposed to lead
-
-
Manually annotated by BRENDA team
Methanococcus sp.
-
-
-
Manually annotated by BRENDA team
Methanothermus sp.
-
-
-
Manually annotated by BRENDA team
swiss mice
-
-
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
animals infected with Trypanosoma evansi
-
-
Manually annotated by BRENDA team
male adult Wistar
-
-
Manually annotated by BRENDA team
SpragueDawley
-
-
Manually annotated by BRENDA team
Wistar (male)
-
-
Manually annotated by BRENDA team
Wistar, male
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
SpragueDawley
-
-
Manually annotated by BRENDA team
Rattus norvegicus Wistar
animals infected with Trypanosoma evansi
-
-
Manually annotated by BRENDA team
mutant strain C-2A'
-
-
Manually annotated by BRENDA team
Schizosaccharomyces sp.
-
-
-
Manually annotated by BRENDA team
cv. Ganga
-
-
Manually annotated by BRENDA team
L. cv. Ganga-5
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
delta-aminolevulinic acid dehydratase-deficient porphyria is a rare enzymatic deficiency of the heme biosynthetic pathway
malfunction
-
delta-ALA-D activity is inhibited in diabetes mellitus, which can result in aminolevulinic acid accumulation that, under physiological relevant conditions, can have pro-oxidant effects. delta-ALA-D activity shows to be correlated with lipid profile indicating that disturbances in lipoproteins metabolism may affect the enzymatic activity
metabolism
-
delta-aminolevulinic acid dehydratase is involved in the heme biosynthetic pathway
metabolism
-
PBGS is a key enzyme in heme biosynthesis
physiological function
-
it is shown that autologous and allogeneic bone marrow transplantation are associated with oxidative stress and that delta-ALA-D activity is a reliable marker for oxidative stress in bone marrow transplantation patients
physiological function
-
delta-aminolevulinate dehydratase is a cytosolic sulfhydryl-containing enzyme that catalyzes the condensation of two molecules of aminolevulinic acid in order to form porphobilinogen, which is the precursor of heme, cytochromes and cobalamines. ALAD plays a role in proteasome S26 activity, which it increases by 75%, overview. The 26S proteasome, a protein complex formed by 32 subunits, performs multiple important proteolytic activities in the cell interacting with the ubiquitination system
physiological function
-
PBGS is a key enzyme in heme biosynthesis that catalyzes the formation of porphobilinogen from two 5-aminolevulinic acid molecules via formation of intersubstrate C-N and C-C bonds
physiological function
-
infection with Trypanosoma evansi is associated with haematocrit, serum levels of iron and zinc and lipid peroxidation. Increased activity of delta-ALA-D in blood occurs in response to the anaemia in remission as heme synthesis is enhanced, iron reduction has a negative correlation with the activity of delta-ALA-D
physiological function
Rattus norvegicus Wistar
-
infection with Trypanosoma evansi is associated with haematocrit, serum levels of iron and zinc and lipid peroxidation. Increased activity of delta-ALA-D in blood occurs in response to the anaemia in remission as heme synthesis is enhanced, iron reduction has a negative correlation with the activity of delta-ALA-D
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
2 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
2 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
2 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
2 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
Rattus norvegicus Wistar
-
-
-
-
?
5-aminolevulinate
?
show the reaction diagram
-
-
-
-
-
5-aminolevulinate
?
show the reaction diagram
-
-
-
-
-
5-aminolevulinate
?
show the reaction diagram
-
during erythropoiesis in chordates the enzyme functions as a part of the heme synthesizing machinery
-
-
-
5-aminolevulinate
?
show the reaction diagram
-
second enzyme in the heme biosynthetic pathway
-
-
-
5-aminolevulinate
?
show the reaction diagram
-
the second and rate-limiting enzyme of the heme-biosynthetic pathway
-
-
-
5-aminolevulinate
?
show the reaction diagram
-
induction by 17beta-estradiol of 5-aminolevulinate
-
-
-
5-aminolevulinate
?
show the reaction diagram
-
enzyme catalyzes the first common step in tetrapyrrole biosynthesis
-
-
-
5-aminolevulinate
?
show the reaction diagram
Q59643
enzyme catalyzes the first common step in tetrapyrrole biosynthesis
-
-
-
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
P0ACB2
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
(3R)-5-aminolevulinate shows a significantly larger isotope effect than (3S)-5-aminolevulinate
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
essential step in tetrapyrrole biosynthesis
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
the enzyme catalyzes the first common step in the biosynthesis of tetrapyrroles
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
the enzyme catalyzes the third step of tetrapyrrole synthesis leading to the formation of heme and chlorophylls in plant tissues. In the light, both 5-aminolevulinate dehydratase activity, and protein level increases 3-4 times compared to the dark-control level. However, no change in the amount of related mRNA is observed. The apparent stability of the mRNA can be due to the abundant expression of a housekeeping gene, which shadows a related gene expressed in the light
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
P13716
the enzyme functions in the first common step in tetrapyrrole biosynthesis
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
the enzyme plays a rate-limiting role in heme biosynthesis of saccharomyces cerevisiae
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
the role of the enzyme may be confined to heme synthesis in the apicoplast that may not account for the total de novo heme biosynthesis in the parasite
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
porphobilinogen synthase catalyzes the first committed step of the tetrapyrrole biosynthesis pathway, enzymatic mechanism starts with formation of a C-C bond, linking C3 of the A-side 5-aminolevulinic acid to C4 of the P-side 5-aminolevulinic acid through an aldole addition
-
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
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
-
-
?
5-aminolevulinic acid + 5-aminolevulinic acid
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
5-aminolevulinic acid + 5-aminolevulinic acid
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
5-aminolevulinic acid + 5-aminolevulinic acid
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
5-aminolevulinic acid + 5-aminolevulinic acid
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
5-aminolevulinic acid + 5-aminolevulinic acid
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
5-aminolevulinic acid + 5-aminolevulinic acid
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
the enzyme stimulates renaturation of luciferase by hsp 70, a member of the heat shock protein 70kDa-family, up to 10fold, the enzyme stimulates renaturation of luciferase by hsp 70 up to 10fold
-
-
-
additional information
?
-
-
the enzyme has a dual role: 1. as 5-aminolevulinate dehydatase, the second enzyme in the pathway of heme synthesis, 2. as CF-2 proteasome inhibitor
-
-
-
additional information
?
-
-
early enzyme of the tetrapyrrole biosynthesis pathway
-
-
-
additional information
?
-
-
direct assay method development with incubation of erythrocyte lysate with the natural substrate, 5-aminolevulinate, followed by quantitative in situ conversion of porphobilinogen to its butyramide and mass spectrometric determination, overview. Using a carbonate buffer rather than phosphate causes nearly a 90% drop in activity and addition of zinc results in a further decrease by up to 35%
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
2 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
2 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
2 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
2 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
-
-
-
?
2 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
Rattus norvegicus Wistar
-
-
-
-
?
5-aminolevulinate
?
show the reaction diagram
-
-
-
-
-
5-aminolevulinate
?
show the reaction diagram
-
-
-
-
-
5-aminolevulinate
?
show the reaction diagram
-
during erythropoiesis in chordates the enzyme functions as a part of the heme synthesizing machinery
-
-
-
5-aminolevulinate
?
show the reaction diagram
-
second enzyme in the heme biosynthetic pathway
-
-
-
5-aminolevulinate
?
show the reaction diagram
-
the second and rate-limiting enzyme of the heme-biosynthetic pathway
-
-
-
5-aminolevulinate
?
show the reaction diagram
-
induction by 17beta-estradiol of 5-aminolevulinate
-
-
-
5-aminolevulinate
?
show the reaction diagram
-
enzyme catalyzes the first common step in tetrapyrrole biosynthesis
-
-
-
5-aminolevulinate
?
show the reaction diagram
Q59643
enzyme catalyzes the first common step in tetrapyrrole biosynthesis
-
-
-
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
essential step in tetrapyrrole biosynthesis
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
the enzyme catalyzes the first common step in the biosynthesis of tetrapyrroles
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
the enzyme catalyzes the third step of tetrapyrrole synthesis leading to the formation of heme and chlorophylls in plant tissues. In the light, both 5-aminolevulinate dehydratase activity, and protein level increases 3-4 times compared to the dark-control level. However, no change in the amount of related mRNA is observed. The apparent stability of the mRNA can be due to the abundant expression of a housekeeping gene, which shadows a related gene expressed in the light
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
P13716
the enzyme functions in the first common step in tetrapyrrole biosynthesis
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
the enzyme plays a rate-limiting role in heme biosynthesis of saccharomyces cerevisiae
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
the role of the enzyme may be confined to heme synthesis in the apicoplast that may not account for the total de novo heme biosynthesis in the parasite
-
?
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
porphobilinogen synthase catalyzes the first committed step of the tetrapyrrole biosynthesis pathway
-
-
?
additional information
?
-
-
the enzyme stimulates renaturation of luciferase by hsp 70 up to 10fold
-
-
-
additional information
?
-
-
the enzyme has a dual role: 1. as 5-aminolevulinate dehydatase, the second enzyme in the pathway of heme synthesis, 2. as CF-2 proteasome inhibitor
-
-
-
additional information
?
-
-
early enzyme of the tetrapyrrole biosynthesis pathway
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
about 80% reactivation of the demetalled protein
Cd2+
-
can restore activity of the apoenzyme
Cd2+
-
inhibition at low concentration of substrate and stimulation at high levels of substrate
Cd2+
-
inhibits enzymatic activity. High molecular weight fraction as well as metallothionein are involved in the detoxification of harmful heavy metals
Co2+
-
about 70% reactivation of the demetalled protein
Co2+
-
about 50% reactivation of the demetalled protein; activates
Co2+
-
partially restores activity after inhibition with EDTA
Cu2+
-
inhibits enzymatic activity. High molecular weight fraction as well as metallothionein are involved in the detoxification of harmful heavy metals
Fe2+
-
partially restores enzyme after inactivation of 2,9-dimethyl-4,7-diphenyl-1,10-phenanthrolinedisulfonate
Fe2+
-
about 70% reactivation of the demetalled protein
K+
-
activates up to 3 mM
K+
-
stimulates, between pH 6.5 and 7.0, K+ is as stimulatory as Mg2+ and the stimulation is almost 2fold
K+
-
stimulates
Li+
-
stimulates
Mg2+
-
required
Mg2+
-
required
Mg2+
-
metal cofactor
Mg2+
-
can not activate the apoenzyme alone, but is able to substitute for the second molar equivalent of bound Zn2+ leading to a further 4fold stimulation
Mg2+
-
activates
Mg2+
-
2 Mg2+ binding sites per subunit; activates; required
Mg2+
-
enzyme utilizes a catalytic MgA present at a stoichiometry of 4/octamer, an allosteric MgC present at a stoichiometry of 8/octamer and a monovalent metal ion, K+
Mg2+
-
binds only 4 Mg2+ per octamer, these 4 Mg2+ allosterically stimulate a metal ion independent catalytic actiovity, in a fashion dependent upon both pH and K+, the allosteric Mg2+ is located in metal binding site C, which is outside the active site. NO evidence is found for metal binding to the potential high-affinity active site metal binding site A and/or B, no direct involvement of Mg2+ in substrate binding and product formation
Mg2+
-
essentail cofactor, allosteric Mg(II) binds with a Kd of 2.5 mM, 2.3fold activation, binding of 3 Mg(II) per subunit
Mg2+
-
4 Zn at metal binding site A , 4 Zn at metal binding site B and 8 Mg at metal binding site C are required for full activity per homooctamer
Mg2+
-
4 Zn at metal binding site A and 8 Mg at metal binding site C are required for full activity per homooctamer
Mg2+
-
Mg(II) causes a twofold stimulation of the Zn(II)-induced activity
Mg2+
-
20-30% stimulation at pH 8.5, no requirement for a metal ion
Mg2+
-
chimeric proteins are constructed 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
Mg2+
-
dependent on
Mg2+
-
can completrly restore activity after inhibition by EDTA; can completrly restore activity after inhibition by EDTA, stabilizes the oligomeric state but is not essential for octamer formation
Mg2+
-
stimulates but is not required for activity. Eight Mg2+ ions can be seen in the crystal structure, one per monomer, all bound at the allosteric magnesium-binding site. No metal ion can be seen in the active site
Mg2+
-
enzyme contains Mg2+ in the active site
Mg2+
-
activates
Mg2+
-
activates
Mg2+
-
implicated in quarternary structure
Mg2+
-
enzyme responds to Mg2+ but not to Zn2+, enzyme shows two Mg2+ affinities
Mg2+
-
activates
Mn2+
-
can reactivate the demetallated protein
Mn2+
-
activates; can reactivate the demetallated protein
Mn2+
-
activates
Na+
-
stimulates
Ni(2+)
-
0.15 mM, activates
Ni(2+)
-
about 70% reactivation of the demetalled protein
Ni2+
-
partially restores activity after inhibition with EDTA
Zinc
-
contains 1 gatom of zinc per mol of subunit, zinc has a structural rather than a direct catalytic role
Zinc
-
binds 8 mol of zinc per mol of octamer, zinc may interact with one or more of the highly reactive enzyme thiol groups
Zinc
-
lacks a catalytic ZnA, enzyme can bind Zn(II), presumably as ZnA, at a stoichiometry of 4/octamer with a Kd of 0.2 mM, this high concentration is outside the physiologically significant range
Zinc
-
4 Zn at metal binding site A , 4 Zn at metal binding site B and 8 Mg at metal binding site C are required for full activity per homooctamer
Zinc
-
4 Zn at metal binding site A and 4 Zn at metal binding site B are required for full activity per homooctamer
Zinc
-
4 Zn at metal binding site A and 8 Mg at metal binding site C are required for full activity per homooctamer
Zinc
-
8 Zn at metal binding site A and 8 Zn at metal binding site B are required for full activity per homooctamer
Zinc
-
Zn(II) metalloenzyme, Zn(II) is required for catalytic activity
Zn2+
-
required
Zn2+
-
optimal activation by 0.1-0.3 mM ZnCl2; required
Zn2+
-
Zn2+ forms a bond with a sulfhydryl group in the enzyme, the octameric enzyme contains 4 gatom of Zn2+ per mol of enzyme, Zn2+ does not participate in substrate binding nor in the maintenance of the quarternary structure of the enzyme
Zn2+
-
activates at 0.1-0.02 mM, inhibits at 1.0 mM
Zn2+
-
activates
Zn2+
-
restores enzyme after inactivation by 2,9-dimethyl-4,7-diphenyl-1,10-phenanthrolinedisulfonate
Zn2+
-
activates; optimal stimulation at 0.1 mM
Zn2+
-
2 mol of Zn2+ bound per mol of subunit; required
Zn2+
-
activity is progressively increased with increasing Zn2+ concentrations up to 0.1 mM, inhibition at high concentrations
Zn2+
-
enzyme uses a catalytic Zn2+
Zn2+
-
the cysteines of the metal switch sequence of the wild-type enzyme bind a catalytic zinc. Chimeric proteins are constructed 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.
Zn2+
-
partially restores activity after inhibition with EDTA
Zn2+
-
-
Zn2+
-
inhibits enzymatic activity
Zn2+
-
required cofactor
Zn2+
-
required for catalysis, bound at the active site
Zn2+
-
delta-ALA-D is a metalloenzyme requiring zinc for activation
Zn2+
-
activates
Mn2+
-
activates
additional information
-
does not require metallic cations for activation
additional information
-
zinc is apparently not a cofactor
additional information
-
no stimulation by Mg2+
additional information
Q6IVV3, -
does not utilize metal ions such as Zn2+ or Mg2+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
-
-
1,10-phenanthroline
-
-
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
-
1 mM, 0.5 mM ZnCl2 protects but does not reverse inhibition. Dithiothreitol protects inhibition by 1 mM 2,3-dimercaptopropane-1-sulfonic acid in a concentration dependent manner
2,3-dimercaptopropane-1-sulfonic acid
-
in presence of Hg2+ or Cd2+ the inhibitory potency increases, no change in inhibitory potency by inclusion of Pb2+, Zn2+ does not modify the inhibitory effect
2,3-dimercaptopropane-1-sulfonic acid
-
0.1 mM, 20% inhibition, more pronounced inhibition in combination with Cd2+
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'-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-chlorolevulinic acid
-
inactivation results fromthe initial formation of a Schiff base with lysine-247, followed by alkylation of lysine-195 by the resulting reactive chloroimide
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
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
-
-
bathocuproine disulfonic acid
-
i.e. 2,9-dimethyl-4,7-diphenyl-1,10-phenanthrolinedisulfonate
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
Cd2+
-
inhibition at low concentration of substrate and stimulation at high levels of substrate
Cd2+
-
inhibits delta-ALA-D activity. Chelating and antioxidant agents potentiated the inhibition
Cd2+
-
enzyme inhibition in excised etiolated leaf segments during greening. Cd2+ inhibits ALAD activity by affecting the ALA binding to the enzyme and/or disrupting thiol interaction. Inhibition of ALAD activity by Cd2+ is decreased in the presence of nitrogenous compounds, glutamine and NH4NO3, overview. Supply of some essential metal ions, such as Mg2+, Zn2+, and Mn2+, also reduces the inhibition of enzyme activity by Cd2+
Co2+
-
above 1 mM
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
-
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
-
incubations of erythrocytes for 24 h with glucose results 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
D-glucose
-
competitive inhibitor for ALA dehydratase
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
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
-
IC50: 0.01 mM
dibutyl diselenide
-
IC50: 0.693 mM, enzyme from liver; IC50: 0.985 mM, enzyme from gill
dicholesteroyl diselenide
-
significant at 0.1 mM
diethyl dicarbonate
-
-
diethyldithiocarbamate
-
-
diphenyl diselenide
-
dithiothreitol protects
diphenyl diselenide
-
IC50: 0.007 mM
diphenyl diselenide
-
IC50: 0.076 mM, enzyme from liver; IC50: 0.274 mM, enzyme from gill
diphenyl diselenide
-
0.0005 mM, 17% inhibition
diphenyl diselenide
-
-
diphenyl diselenide
-
significantl inhibition
diphenyl diselenide
-
significant at 0.001 mM
diphenyl ditelluride
-
dithiothreitol protects
DTNB
-
reversible loss of activity
ebselen
-
dithiothreitol protects
EDTA
-
no inhibition
EDTA
-
0.1 mM, slight
EDTA
-
5 mM, 90% inhibition
EDTA
-
activity can be completely restored by addition of Mg2+ or Mn2+. Co2+, Zn2+, and Ni2+ partially restore EDTA-inhibited activity
EDTA
-
0.3 mM, 51% inhibition
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
Hg2+
-
inhibits enzyme in vivo at 6 h and 12 h after treatment. Se4+ abolishes the inhibitory effect of Hg2+
Hg2+
-
inhibitory effect is increased by meso-2,3-dimercaptosuccinic acid, inhibition is prevented by dithiothreitol
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
-
irreversible
iodoacetamide
-
insensitive
iodoacetamide
-
1 mM, 97% inhibition
iodoacetate
-
irreversible
levulinic acid
-
competitive
levulinic acid
-
-
levulinic acid
-
-
levulinic acid
-
a weak competitive inhibitor
Mercury ions
-
-
-
meso-2,3-dimercaptosuccinic acid
-
4 mM, 1 mM ZnCl2 protects but does not reverse inhibition. Dithiothreitol protects inhibition by 1 mM meso-2,3-dimercaptosuccinic acid in a concentration dependent manner
meso-2,3-dimercaptosuccinic acid
-
in presence of Hg2+ or Cd2+ the inhibitory potency increases, Zn2+ does not modify the inhibitory effect
meso-2,3-dimercaptosuccinic acid
-
0.1 mM, 18% inhibition
methyl methanethiosulfonate
-
-
Mn2+
-
above 1 mM
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
NaCN
-
in presence of the substrate
NEM
-
1 mM, 85% inhibition
Neocuproine
-
2,9-dimethyl-1,10-phenanthroline
p-hydroxymercuribenzoate
-
-
Pb2+
-
does not produce a change in the quarternary structure detectable by small angle X-ray scattering
Pb2+
-
noncompetitive
Pb2+
-
5-aminolevulinate protects
Pb2+
-
reversed by Zn2+
PCMB
-
1 mM, 97% inhibition
phenyl selenoacetylene
-
IC50: above 0.4 mM
phenyl selenoacetylene
-
IC50: 0.25 mM
phenyl selenoacetylene
-
inhibition involves conversion of phenyl selenoacetylene to diphenyl diselenide, that induces oxidation of essential -SH groups of the enzyme. Inhibition is partially prevented by incubation under argon atmosphere and is completely prevented by dithiothreitol
phenyl selenoxideacetylene
-
IC50: 0.1 mM, inhibition is antagonized by dithiothreitol
phenyl selenoxideacetylene
-
IC50: 0.045 mM, inhibition is antagonized by dithiothreitol
phosphate
-
competitive against Mg2+
protoporphyrin IX
-
-
pyridoxal 5'-phosphate
-
competitive
pyridoxal 5'-phosphate
-
30% inhibition at 1 mM, negligible inhibition at 0.05 mM
pyridoxal phosphate
-
-
pyridoxamine phosphate
-
-
rac-2-hydroxy-4-oxopentanoic acid
-
-
-
rac-3-hydroxy-4-oxopentanoic acid
-
-
-
sodium selenide
-
IC50: 0.005 mM
sodium selenide
-
IC50: 0.386 mM, enzyme from gill; IC50: 0.902 mM, enzyme from liver
succinic acid
-
noncompetitive
succinic acid monomethyl ester
-
competitive
succinylacetone
-
-
succinylacetone
-
50% inhibition by 125 nM
succinylacetone
-
50% inhibition by 250 nM
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
Zn2+
-
activates at 0.1-0.02 mM, inhibits at 1.0 mM
Zn2+
-
activity is progressively increased with increasing Zn2+ concentrations up to 0.1 mM, inhibition at high concentrations
Zn2+
-
the inhibitory zinc is located at a subunit interface using Cys219 and His10 as ligands
Zn2+
-
pH 7.5, 50% inhibition at 0.12 mM
Zn2+
-
at pH 8.5, 50% inhibition by 0.075 mM. At pH 7.5, 50% inhibition by less than 0.02 mM
Zn2+
-
exocenous addition of zinc results in a decrease by up to 35% in enzyme activity
additional information
-
insensitive to inhibition by hemin and protoporphyrin
-
additional information
-
no inhibition by EDTA even at 25 mM
-
additional information
-
the enzyme from human erythrocytes is a potential target for organochalcogens
-
additional information
Q6IVV3, -
no inhibition by 10 mM EDTA or 1,20-phenanthroline
-
additional information
-
no inhibition by dicholesteroyl diselenide
-
additional information
-
in vivo iron reduction in rat blood has a negative correlation with the activity of delta-ALA-D, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
thiol
-
20 mM, essential to maintain the enzyme in its reduced state
thiol
-
required
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.043
-
5-aminolevulinate
-
-
0.061
-
5-aminolevulinate
-
shell gland enzyme
0.077
-
5-aminolevulinate
-
-
0.1
-
5-aminolevulinate
-
-
0.108
-
5-aminolevulinate
-
pH 8
0.15
-
5-aminolevulinate
-
partially purified enzyme
0.158
-
5-aminolevulinate
-
-
0.2
-
5-aminolevulinate
-
liver enzyme
0.208
-
5-aminolevulinate
-
pH 8.5
0.26
-
5-aminolevulinate
-
-
0.27
-
5-aminolevulinate
-
-
0.287
-
5-aminolevulinate
-
-
0.294
-
5-aminolevulinate
-
pH 7.5
0.33
-
5-aminolevulinate
-
pH 8.6 in Na-Hepes buffer
0.333
-
5-aminolevulinate
-
pH 6.8, 37C
0.359
-
5-aminolevulinate
-
-
0.7
-
5-aminolevulinate
-
in presence of 2-mercaptoethanol
0.8
-
5-aminolevulinate
-
-
0.8
-
5-aminolevulinate
-
at pH 6 and pH 8.5
0.8
-
5-aminolevulinate
-
at pH 7.5
1
-
5-aminolevulinate
-
at pH 6.8
1
-
5-aminolevulinate
-
at pH 9
2
-
5-aminolevulinate
-
in absence of 2-mercaptoethanol
0.00032
-
5-aminolevulinic acid
-
-
0.02
-
5-aminolevulinic acid
-
wild type, pH 9, octamer
0.15
-
5-aminolevulinic acid
-
-
0.2
-
5-aminolevulinic acid
-
wild type, pH 7, almost octamer
0.65
-
5-aminolevulinic acid
-
expressed from expression vector pET28a+
2.1
-
5-aminolevulinic acid
-
expressed from expression vector pET28a+, His-tag removed
3.22
-
5-aminolevulinic acid
-
expressed from expression vector pLM1
4.5
-
5-aminolevulinic acid
-
wild type, pH 9, predominantly hexamer and/or dimer
4.6
-
5-aminolevulinic acid
-
F12L, pH 9
18
-
5-aminolevulinic acid
-
F12L, pH 7
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]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
16.1
-
5-aminolevulinic acid
-
-
additional information
-
additional information
-
-
-
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
50300
-
5-aminolevulinic acid
-
-
5117
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
-
5,5'-iminobis(4-oxopentanoic acid)
-
-
0.313
-
5,5'-iminobis(4-oxopentanoic acid)
-
37C, pH 8.5
0.098
-
5,5'-oxybis(4-oxopentanoic acid)
-
-
0.963
-
5,5'-oxybis(4-oxopentanoic acid)
-
37C, pH 8.5
9.94
-
5,5'-sulfinylbis(4-oxopentanoic acid)
-
37C, pH 8.5
10.8
-
5,5'-sulfinylbis(4-oxopentanoic acid)
-
-
0.342
-
5,5'-sulfonylbis(4-oxopentanoic acid)
-
37C, pH 8.5
11
-
5,5'-sulfonylbis(4-oxopentanoic acid)
-
-
0.06
-
5,5'-thiobis(4-oxopentanoic acid)
-
-
38.4
-
5,5'-thiobis(4-oxopentanoic acid)
-
37C, pH 8.5
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
-
-
0.03
-
diethyl dicarbonate
-
-
0.96
-
levulinic acid
-
-
1.5
-
levulinic acid
-
-
0.0025
-
protoporphyrin IX
-
-
0.03
-
pyridoxal phosphate
-
-
9
-
succinic acid
-
-
1.9
-
succinic acid monomethyl ester
-
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
30
-
1-amino-4-methoxy-2-butanone
-
-
32.5
-
1-amino-5-hydroxy-2-pentanone
-
-
0.31
-
5,5'-iminobis(4-oxopentanoic acid)
-
-
0.96
-
5,5'-oxybis(4-oxopentanoic acid)
-
-
38
-
5,5'-sulfinylbis(4-oxopentanoic acid)
-
-
9.9
-
5,5'-sulfonylbis(4-oxopentanoic acid)
-
-
0.34
-
5,5'-thiobis(4-oxopentanoic acid)
-
-
0.01
-
7-(3-aminopentan-3-yl)-5-chloroquinolin-8-ol
-
-
0.319
-
Al3+
-
IC50: 0.319 mM, GSH has no protective effect
1.33
-
alaremycin
-
-
0.0345
-
Cd2+
-
pH 6.8, 37C
0.01
-
dibutyl diselenide
-
IC50: 0.01 mM
0.693
-
dibutyl diselenide
-
IC50: 0.693 mM, enzyme from liver
0.985
-
dibutyl diselenide
-
IC50: 0.985 mM, enzyme from gill
0.00195
-
diphenyl diselenide
-
37C, pH 6.5
0.007
-
diphenyl diselenide
-
IC50: 0.007 mM
0.076
-
diphenyl diselenide
-
IC50: 0.076 mM, enzyme from liver
0.274
-
diphenyl diselenide
-
IC50: 0.274 mM, enzyme from gill
0.442
-
Ga3+
-
inhibits by competing with Zn2+, IC50: 0.442 mM, GSH has no protective effect, Zn2+ completely recovers inhibition
0.298
-
In3+
-
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
-
-
0.0056
-
Pb2+
-
37C, pH 8.5
0.0062
-
Pb2+
-
37C, pH 6.5
0.25
-
phenyl selenoacetylene
-
IC50: 0.25 mM
0.4
-
phenyl selenoacetylene
-
IC50: above 0.4 mM
0.045
-
phenyl selenoxideacetylene
-
IC50: 0.045 mM, inhibition is antagonized by dithiothreitol
0.1
-
phenyl selenoxideacetylene
-
IC50: 0.1 mM, inhibition is antagonized by dithiothreitol
0.005
-
sodium selenide
-
IC50: 0.005 mM
0.386
-
sodium selenide
-
IC50: 0.386 mM, enzyme from gill
0.902
-
sodium selenide
-
IC50: 0.902 mM, enzyme from liver
0.001
-
succinylacetone
-
-
0.0085
-
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
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
-
-
-
0.4
-
-
-
0.63
-
-
-
0.67
-
-
wild-type octamer
4.33
-
-
-
6.98
-
-
shell gland enzyme
10.3
-
-
liver enzyme
additional information
-
-
specific and sensitive coupled-enzyme assay
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
6.7
-
-
6.3
-
-
-
6.5
-
-
-
6.8
-
-
-
6.8
-
-
wild-type enzyme
6.8
-
-
assay at
6.8
-
-
assay at
7.5
8.5
-
-
7.7
9.2
-
-
8
8.6
-
in citrate buffer, Tris-maleate buffer, imidazole buffer and Tris buffer
8
-
-
assay at
8.5
-
-
two pH-optima at pH 8.5 and at pH 9.4
8.5
-
Q6IVV3, -
-
8.5
-
-
-
8.6
-
-
in presence of Mg2+ and K+
9.4
-
-
two pH-optima at pH 8.5 and at pH 9.4
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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 OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
39
-
-
assay at
65
-
-
-
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
75
-
37C: about 30% of maximal activity, 75C: about 90% of maximal activity
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.4
-
-
isoelectric focusing, pH-range 3-10
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
delta-ALA-D activity in patients with chronic renal failure with hemodialysis treatment and in patients not undergoing hemodialysis is lower when compared to the control group. delta-ALA-D activity correlates positively with hemoglobin content
Manually annotated by BRENDA team
-
delta-ALA-D activity is decreased in situations associated to hyperglycemia maintained for long periods. Hypofunction of the thyroid gland, when non-compensated, increase the activity of delta-ALA-D
Manually annotated by BRENDA team
-
plasma ALA level of the fatigued rats is slightly higher (approximately 1.4fold) than that of the control or food-restricted animals
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
plasma ALA level of the fatigued rats is slightly higher (approximately 1.4fold) than that of the control or food-restricted animals
-
Manually annotated by BRENDA team
-
mercury decreases porphobilinogen-synthase activity
Manually annotated by BRENDA team
-
delta-aminolevulinate dehydratase activity is lower in hemodialysis patients compared to control
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
-
-
Manually annotated by BRENDA team
-
Friend erythroleukemia cell line 586
Manually annotated by BRENDA team
-
mercury decreases porphobilinogen-synthase activity
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
etiolated
Manually annotated by BRENDA team
-
mercury decreases porphobilinogen-synthase activity
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
maximal activity before pigmentation of the egg shell
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
in the urine of the fatigued rats, the ALA level increases (approximately 2fold) as compared with that of the control rats
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
in the urine of the fatigued rats, the ALA level increases (approximately 2fold) as compared with that of the control rats
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
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)
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
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
-
Q6IVV3, -
gel filtration, analytical ultracentrifugation
240000
-
-
gel filtration
244000
-
-
wild-type enzyme, equilibrium sedimentation
244000
-
-
wild-type enzyme, pH 7, analytical ultracentrifugation
252000
-
-
gel filtration
260000
-
-
sucrose density gradient centrifugation
260000
-
-
low-speed equilibrium sedimentation
270000
-
-
gel filtration
275000
-
-
glycerol density gradient centrifugation
280000
-
-
gel filtration
280000
-
-
gel filtration
280000
-
-
gel filtration
280000
-
-
-
282000
-
-
measurement of sedimentation velocity
282000
-
-
gel filtration
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
-
-
the enzyme is incorporated into mitochondria at a size of 170000 Da and then is gradually converted to a size of 110000 Da, within the mitochondria, hemin stimulates the aggregation of the enzyme in cytosol to a size of 700000 Da
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 38000, SDS-PAGE
?
-
x * 45000, SDS-PAGE
?
-
x * 37000, maximally active octamer can dissociate into less active smaller subunits, minimal functional unit is a tetramer, SDS-PAGE
dimer
-
pro-hexamer dimer and pro-octamer dimer, analyzed by gel filtration
dimer
-
-
dimer
-
recombinant TgPBGS also shows low levels of dimers, 2 * 40000 Da, SDS-PAGE
hexamer
-
6 * 50000, SDS-PAGE
hexamer
-
6 * 40000, SDS-PAGE
hexamer
-
6 * 42000, SDS-PAGE
hexamer
Q6IVV3, -
6 * 35856, calculation from nucleotide sequence
hexamer
-
wild type, pH 8.8, catalytic turnover favors octamer, analyzed by gel filtration and anion exchange chromatography
hexamer
-
hexameric structure of the enzyme only shows low activity. 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
octamer
-
8 * 35000, SDS-PAGE
octamer
-
8 * 35000, SDS-PAGE
octamer
-
8 * 31000, SDS-PAGE
octamer
-
8 * 36000, SDS-PAGE
octamer
-
8 * 34900, equilibrium sedimentation in presence of 6 M guanidine-HCl; 8 * 35000, SDS-PAGE
octamer
-
8 * 30000, SDS-PAGE
octamer
-
8 * 36000, SDS-PAGE
octamer
-
8 * 37000, SDS-PAGE
octamer
-
8 * 43000, SDS-PAGE
octamer
-
8 * 38000, mature recombinant enzyme, SDS-PAGE
octamer
-
8 * 46000, mature recombinant enzyme, SDS-PAGE
octamer
-
6 * 37832, electrospray ionization mass spectrometry
octamer
-
the enzyme is an obligate oligomer that can exist in functionally distinct quaternary states of different stoichiometries, which are called morpheeins, human PBGS assembles into long-lived morpheeins and is capable of forming either a high activity octamer or a low activity hexamer
octamer
-
wild type, pH 6.9 and pH 8.8, analyzed by gel filtration and anion exchange chromatography
octamer
-
high activity octamer is the dominant assembly
octamer
-
recombinant TgPBGS is purified as a stable octamer, 8 * 40000 Da, SDS-PAGE
hexamer or octamer
-
by analytical ultracentrifugation
additional information
-
dissociation and reassociation of the subunits of immobilized PGB synthase
additional information
-
-
additional information
-
wild-type enzyme and variant F12L exist in different oligomeric states. The wild-type enzyme exists as an octamer and the F12L variant exists as a hexamer. It appears that any equilibrium between octamer and hexamer most probably proceeds through the interconversion of hugging dimer and the detached dimer
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
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
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
9
-
-
highest stability at
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
50
-
-
200 min, 50% inactivation
50
-
-
15 min, 63% loss of activity
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 ACCESSION NO.
LITERATURE
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
-
EGTA prevents proteolysis
-
OXIDATION STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
total but reversible loss of activity by O2
-
210686
sensitive to oxygen, t1/2: 135 min, the oxygen-inactivated enzyme is restored to full activity by incubation with thiols
-
210688
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
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 ACCESSION NO.
LITERATURE
two-step purification
-
using affinity chromatography and anion-exchange chromatography
-
native enzyme by ammonium sulfate fractionation, anion exchange chromatography, and gel filtration
-
apparent homogeneity (analyzed by SDS-PAGE)
-
recombinant
Q6IVV3, -
using Ni-NTA chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
His-tagged
-
expression in Escherichia coli
-
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 in Escherichia coli
-
structure of 5-aminolaevulinic acid dehydratase complexed with the irreversible inhibitor 4,7-dioxosebacic acid
-
expressed in Escherichia coli as a His-tagged fusion protein
-
expression in Escherichia coli
-
hexa-His-tag, removed by cleavage with thrombin
-
expression in Escherichia coli
Q6IVV3, -
recombinant TgPBGS is expressed in Escherichia coli as a His-tagged fusion protein
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
E89K
-
75% of wild-type activity
E89K
-
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
F12L
-
the catalytic activity is very low under conditions at which the wild-type human enzyme is most active
F12L
-
naturally occurring variant
F12L
-
enzyme activity undetectable
F12L
-
low activity mutant F12L shows a hexameric structure, mutant F12L is used for in silico screening of 111000 structures for hexamer-stabilizing inhibitors
G133R
-
11% of wild-type activity
K59N
-
112% of wild-type activity
K59N/G133R
-
22% of wild-type activity
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
L273R
-
enzyme activity undetectable
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 ACCESSION NO.
COMMENTARY
LITERATURE
analysis
-
indirect measurement of blood lead in human subjects; measurement of ethanol consumption in alcoholics
diagnostics
-
the DELTA-aminolevulinic acid dehydratase test of blood is valid and representative for low-level as well as long-term exposure to lead. The test might be applicable to diagnostic purposes and screening of the population having been exposed to low-level lead over a long-term period
diagnostics
-
the enzyme activity is a diagnostic marker for the clinical diagnosis of delta-aminolevulinic acid dehydratase-deficient porphyria, a rare enzymatic deficiency of the heme biosynthetic pathway
medicine
-
delta-ALA-D activity is a reliable marker for oxidative stress in bone marrow transplantation patients