Any feedback?
Please rate this page
(enzyme.php)
(0/150)

BRENDA support

BRENDA Home
show all | hide all No of entries

Information on EC 4.2.1.24 - porphobilinogen synthase and Organism(s) Escherichia coli and UniProt Accession P0ACB2

for references in articles please use BRENDA:EC4.2.1.24
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
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.
Specify your search results
Select one or more organisms in this record: ?
This record set is specific for:
Escherichia coli
UNIPROT: P0ACB2
Show additional data
Do not include text mining results
Include (text mining) results
Include results (AMENDA + additional results, but less precise)
Word Map
hide
The taxonomic range for the selected organisms is: Escherichia coli
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
hide
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
5-aminolevulinate hydro-lyase (adding 5-aminolevulinate and cyclizing)
-
-
-
-
5-aminolevulinic acid dehydrase
-
-
-
-
5-aminolevulinic acid dehydratase
-
-
-
-
5-levulinic acid dehydratase
-
-
-
-
ALAD
-
-
-
-
ALADH
-
-
-
-
aminolevulinate dehydrase
-
-
-
-
aminolevulinate dehydratase
-
-
-
-
aminolevulinic dehydratase
-
-
-
-
delta-ALAD
-
-
-
-
delta-aminolevulinate dehydrase
-
-
-
-
delta-aminolevulinate dehydratase
-
-
-
-
delta-aminolevulinic acid dehydrase
-
-
-
-
delta-aminolevulinic acid dehydratase
-
-
-
-
delta-aminolevulinic dehydratase
-
-
-
-
gamma-aminolevulinic acid dehydratase
-
-
-
-
Porphobilinogen synthase
-
-
-
-
porphobilinogen synthetase
-
-
-
-
synthase, porphobilinogen
-
-
-
-
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
5-aminolevulinate + 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
5-aminolevulinate + 5-aminolevulinate
porphobilinogen + 2 H2O
show the reaction diagram
essential step in tetrapyrrole biosynthesis
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zn2+
enzyme uses a catalytic Zn2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4,7-dioxosebaic acid
-
4-oxosebaic acid
active site-directed irreversible inhibitor, less potent than 4,7-dioxosebaic acid
levulinic acid
-
1,10-phenanthroline
-
-
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
D-glucose
-
-
D-xylose
-
-
methyl methanethiosulfonate
-
-
protoporphyrinogen IX
-
feedback inhibition by downstream intermediate
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.8 - 1
5-aminolevulinate
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 8
-
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
270000
-
gel filtration
36000
-
8 * 36000, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
octamer
-
8 * 36000, SDS-PAGE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure of enzyme complexed with 4-oxosebaic acid and of enzyme complexed with 4,7-dioxosebaic acid
high-resolution structure of the enzyme cocrystallized with a noncovalently bound moiety of the product, porphobilinogen. The pyrrole side-chain amino group is datively bound to the active-site zinc ion and the porphobilinogen carboxylates interact with the enzyme via hydrogen bonds and salt bridges with invariant residues. Comparison of substrate and product complexes from humans, Escherichia coli and the hyperthermophile Pyrobaculum calidifontis
X-ray structure of the enzyme complexed with the inhibitor levulinic acid at 2.0 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
Mg2+ stabilizes the quarternary structure of the protein
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
His-tagged
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
synthesis
-
in addition to hemA and hemL, hemB, hemD, hemF, hemG and hemH are also major regulatory targets of the heme biosynthesis pathway. Up-regulation of hemD and hemF benefits ALA accumulation whereas overexpression of hemB, hemG and hemH diminishes ALA accumulation. By combinatorial overexpression of hemA, hemL,hemD and hemF with different copy-number plasmids, the titer of ALA can be improved to 3.25 g/l
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Erskine, P.T.; Norton, E.; Cooper, J.B.; Lambert, R.; Coker, A.; Lewis, G.; Spencer, P.; Sarwar, M.; Wood, S.P.; Warren, M.J.; Shoolingin-Jordan, P.M.
X-ray structure of 5-aminolevulinic acid dehydratase from Escherichia coli complexed with the inhibitor levulinic acid at 2.0 A resolution
Biochemistry
38
4266-4276
1999
Escherichia coli (P0ACB2), Escherichia coli
Manually annotated by BRENDA team
Spencer, P.; Jordan, P.M.
Purification and characterization of 5-aminolevulinic acid dehydratase from Escherichia coli and a study of the reactive thiols at the metal-binding domain
Biochem. J.
290
279-287
1993
Escherichia coli
Manually annotated by BRENDA team
Jaffe, E.K.; Ali, S.; Mitchell, L.W.; Taylor, K.M.; Volin, M.; Markham, G.D.
Characterization of the role of the stimulatory magnesium of Escherichia coli porphobilinogen synthase
Biochemistry
34
244-251
1995
Escherichia coli
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
Mitchell, L.W.; Jaffe, E.K.
Porphobilinogen synthase from Escherichia coli is a Zn(II) metalloenzyme stimulated by Mg(II)
Arch. Biochem. Biophys.
300
169-177
1993
Escherichia coli
Manually annotated by BRENDA team
Shoolingin-Jordan, P.M.; Spencer, P.; Sarwar, M.; Erskine, P.E.; Cheung, K.M.; Cooper, J.B.; Norton, E.B.
5-Aminolaevulinic acid dehydratase: metals, mutants and mechanism
Biochem. Soc. Trans.
30
584-590
2002
Escherichia coli
Manually annotated by BRENDA team
Jaffe, E.K.; Kervinen, J.; Martins, J.; Stauffer, F.; Neier, R.; Wlodawer, A.; Zdanov, A.
Species-specific inhibition of porphobilinogen synthase by 4-oxosebacic acid
J. Biol. Chem.
277
19792-19799
2002
Escherichia coli (P0ACB2), Escherichia coli
Manually annotated by BRENDA team
Lin, J.; Fu, W.; Cen, P.
Characterization of 5-aminolevulinate synthase from Agrobacterium radiobacter, screening new inhibitors for 5-aminolevulinate dehydratase from Escherichia coli and their potential use for high 5-aminolevulinate production
Biores. Technol.
100
2293-2297
2009
Escherichia coli, Escherichia coli Rosetta(DE3)
Manually annotated by BRENDA team
Mills-Davies, N.; Butler, D.; Norton, E.; Thompson, D.; Sarwar, M.; Guo, J.; Gill, R.; Azim, N.; Coker, A.; Wood, S.; Erskine, P.; Coates, L.; Cooper, J.; Rashid, N.; Akhtar, M.; Shoolingin-Jordan, P.
Structural studies of substrate and product complexes of 5-aminolaevulinic acid dehydratase from humans, Escherichia coli and the hyperthermophile Pyrobaculum calidifontis
Acta Crystallogr. Sect. D
73
9-21
2017
Pyrobaculum calidifontis (A3MWV9), Pyrobaculum calidifontis, Escherichia coli (P0ACB2), Escherichia coli, Homo sapiens (P13716), Homo sapiens, Pyrobaculum calidifontis JCM 11548 (A3MWV9)
Manually annotated by BRENDA team
Zhang, J.; Kang, Z.; Chen, J.; Du, G.
Optimization of the heme biosynthesis pathway for the production of 5-aminolevulinic acid in Escherichia coli
Sci. Rep.
5
8584
2015
Escherichia coli
Manually annotated by BRENDA team