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Information on EC 4.2.1.24 - porphobilinogen synthase and Organism(s) Saccharomyces cerevisiae and UniProt Accession P05373

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EC Tree
     4 Lyases
         4.2 Carbon-oxygen lyases
             4.2.1 Hydro-lyases
                4.2.1.24 porphobilinogen synthase
IUBMB Comments
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.
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Saccharomyces cerevisiae
UNIPROT: P05373
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The taxonomic range for the selected organisms is: Saccharomyces cerevisiae
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
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2
5-aminolevulinate
=
porphobilinogen
+
2
H2O
2
=
+
2
Synonyms
delta-aminolevulinic acid dehydratase, ala-d, pbgs, delta-ala-d, delta-aminolevulinate dehydratase, ala dehydratase, porphobilinogen synthase, ala synthetase, 5-aminolevulinic acid dehydratase, delta-alad, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5-aminolevulinate dehydrase
-
-
-
-
5-aminolevulinate dehydratase
-
-
-
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5-aminolevulinate hydro-lyase (adding 5-aminolevulinate and cyclizing)
-
-
-
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5-aminolevulinic acid dehydrase
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-
-
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5-aminolevulinic acid dehydratase
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-
-
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5-levulinic acid dehydratase
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-
-
-
ALAD
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-
-
-
ALADH
-
-
-
-
aminolevulinate dehydrase
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-
-
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aminolevulinate dehydratase
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aminolevulinic dehydratase
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-
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delta-ALAD
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-
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delta-aminolevulinate dehydrase
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delta-aminolevulinate dehydratase
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delta-aminolevulinic acid dehydrase
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delta-aminolevulinic acid dehydratase
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-
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delta-aminolevulinic dehydratase
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-
-
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gamma-aminolevulinic acid dehydratase
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-
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Porphobilinogen synthase
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-
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porphobilinogen synthetase
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-
-
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synthase, porphobilinogen
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-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
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
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
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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
-
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 + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
NATURAL SUBSTRATE
NATURAL 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 + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
-
the enzyme plays a rate-limiting role in heme biosynthesis of saccharomyces cerevisiae
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zinc
8 Zn at metal binding site A and 8 Zn at metal binding site B are required for full activity per homooctamer
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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
Zn2+
-
activity is progressively increased with increasing Zn2+ concentrations up to 0.1 mM, inhibition at high concentrations
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.359
5-aminolevulinate
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
-
PBGS is a key enzyme in heme biosynthesis
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
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
275000
-
glycerol density gradient centrifugation
37000
-
8 * 37000, SDS-PAGE
additional information
-
-
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
octamer
-
8 * 37000, SDS-PAGE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
50
-
15 min, 63% loss of activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Shemin, D.
delta-Aminolevulinic acid dehydratase
The Enzymes, 3rd Ed. (Boyer, P. D. , ed. )
7
323-337
1972
Bos taurus, Saccharomyces cerevisiae, Gallus gallus, Oryctolagus cuniculus, Homo sapiens, Mus musculus, Nicotiana tabacum, Rattus norvegicus, Rhodobacter capsulatus, Cereibacter sphaeroides, Triticum aestivum
-
Manually annotated by BRENDA team
Borralho, L.M.; Ortiz, C.H.D.; Panek, A.D.; Mattoon, J.R.
Purification of delta-aminolevulinate dehydratase from genetically engineered yeast
Yeast
6
319-330
1990
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Jaffe, E.K.
The porphobilinogen synthase family of metalloenzymes
Acta Crystallogr. Sect. D
56
115-128
2000
Actinobacillus sp., Synechocystis sp., Aquifex sp., Archaeoglobus sp., Bordetella sp., Bradyrhizobium sp., Campylobacter sp., Candida sp. (in: Saccharomycetales), Caulobacter sp., Streptomyces sp., Chlamydia sp., Chlamydomonas sp., Clostridium sp., Deinococcus sp., Escherichia coli, Helicobacter sp., Homo sapiens, Methanobacterium sp., Methanococcus sp., Methanothermus sp., Mycobacterium sp., Neisseria sp., Physcomitrella sp., Pisum sativum, Propionibacterium sp., Rattus norvegicus, Rhodobacter sp., Rickettsia sp., Salmonella sp., Schizosaccharomyces sp., Shewanella sp., Vibrio sp., Yersinia sp., Saccharomyces cerevisiae (P05373), Pseudomonas aeruginosa (Q59643)
Manually annotated by BRENDA team
Hoffman, M.; Gora, M.; Rytka, J.
Identification of rate-limiting steps in yeast heme biosynthesis
Biochem. Biophys. Res. Commun.
310
1247-1253
2003
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Erskine, P.T.; Coates, L.; Butler, D.; Youell, J.H.; Brindley, A.A.; Wood, S.P.; Warren, M.J.; Shoolingin-Jordan, P.M.; Cooper, J.B.
X-ray structure of a putative reaction intermediate of 5-aminolevulinic acid dehydratase
Biochem. J.
373
733-738
2003
Saccharomyces cerevisiae (P05373), Saccharomyces cerevisiae
Manually annotated by BRENDA team
Erskine, P.T.; Coates, L.; Newbold, R.; Brindley, A.A.; Stauffer, F.; Beaven, G.D.; Gill, R.; Coker, A.; Wood, S.P.; Warren, M.J.; Shoolingin-Jordan, P.M.; Neier, R.; Cooper, J.B.
Structure of yeast 5-aminolaevulinic acid dehydratase complexed with the inhibitor 5-hydroxylaevulinic acid
Acta Crystallogr. Sect. D
61
1222-1226
2005
Saccharomyces cerevisiae (P05373), Saccharomyces cerevisiae
Manually annotated by BRENDA team
Erdtman, E.; Bushnell, E.A.; Gauld, J.W.; Eriksson, L.A.
Computational insights into the mechanism of porphobilinogen synthase
J. Phys. Chem. B
114
16860-16870
2010
Saccharomyces cerevisiae
Manually annotated by BRENDA team