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Information on EC 1.3.1.76 - precorrin-2 dehydrogenase
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1.3.1.76 precorrin-2 dehydrogenaseIUBMB Comments
This enzyme catalyses the second of three steps leading to the formation of siroheme from uroporphyrinogen III. The first step involves the donation of two S-adenosyl-L-methionine-derived methyl groups to carbons 2 and 7 of uroporphyrinogen III to form precorrin-2 (EC 2.1.1.107, uroporphyrin-III C-methyltransferase) and the third step involves the chelation of ferrous iron to sirohydrochlorin to form siroheme (EC 4.99.1.4, sirohydrochlorin ferrochelatase). In Saccharomyces cerevisiae, the last two steps are carried out by a single bifunctional enzyme, Met8p. In some bacteria, steps 1-3 are catalysed by a single multifunctional protein called CysG, whereas in Bacillus megaterium, three separate enzymes carry out each of the steps, with SirC being responsible for the above reaction.
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Word Map
- 1.3.1.76
- uroporphyrinogen
-
sirohaem
-
dehydrogenation
-
ferrochelation
- sirohydrochlorin
-
prosthetic
- cobalamin
- cobalt
- tetrapyrrole
- nitrite
-
nad+-dependent
- megaterium
- sulfite
- sulfur
- reductases
-
methylase
-
transmethylase
-
renamed
- typhimurium
- synthases
-
s-adenosyl-l-methionine-dependent
- cobaltochelatase
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
met8p, siroheme synthase, precorrin-2 dehydrogenase, cysg enzyme, cysg gene product, 
more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CysG
CysG2
EC 2.1.1.107
-
multifunctional protein, first of three steps leading to formation of siroheme from uroporphyrinogen III
Met8p
P2D
precorrin-2 dehydrogenase
S-adenosyl-L-methionine(SAM)-dependent bismethyltransferase, dehydrogenase and ferrochelatase
-
-
SirC
siroheme synthetase
multifunctional protein catalyzing all 3 final steps leading to siroheme from uroporphyrinogen III
CysG
-
-
-
-
Met8p
-
-
-
-
SirC
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
precorrin-2 + NAD+ = sirohydrochlorin + NADH + H+
first step
-
-
-
precorrin-2 + NAD+ = sirohydrochlorin + NADH + H+
This enzyme catalyses the second of three steps leading to the formation of siroheme from uroporphyrinogen III. The first step involves the donation of two S-adenosyl-L-methionine-derived methyl groups to carbons 2 and 7 of uroporphyrinogen III to form precorrin-2 (EC 2.1.1.107, uroporphyrin-III C-methyltransferase) and the third step involves the chelation of ferrous iron to sirohydrochlorin to form siroheme (EC 4.99.1.4, sirohydrochlorin ferrochelatase). In Saccharomyces cerevisiae, the last two steps are carried out by a single bifunctional enzyme, Met8p. In some bacteria, steps 1-3 are catalysed by a single multifunctional protein called CysG, whereas in Bacillus megaterium, three separate enzymes carry out each of the steps, with SirC being responsible for the above reaction
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
KEGG
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SYSTEMATIC NAME
IUBMB Comments
precorrin-2:NAD+ oxidoreductase
This enzyme catalyses the second of three steps leading to the formation of siroheme from uroporphyrinogen III. The first step involves the donation of two S-adenosyl-L-methionine-derived methyl groups to carbons 2 and 7 of uroporphyrinogen III to form precorrin-2 (EC 2.1.1.107, uroporphyrin-III C-methyltransferase) and the third step involves the chelation of ferrous iron to sirohydrochlorin to form siroheme (EC 4.99.1.4, sirohydrochlorin ferrochelatase). In Saccharomyces cerevisiae, the last two steps are carried out by a single bifunctional enzyme, Met8p. In some bacteria, steps 1-3 are catalysed by a single multifunctional protein called CysG, whereas in Bacillus megaterium, three separate enzymes carry out each of the steps, with SirC being responsible for the above reaction.
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CAS REGISTRY NUMBER
COMMENTARY
227184-47-6
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
sirohydrochlorin + Fe2+
siroheme + H+
-
-
-
?
additional information
?
-
-
large multifunctional protein that catalyzes four diverse reactions, 2 S-adensyl-L-methionine-dependent methylations, NAD+-dependent tetrapyrrole dehydrogenation and metal chelation
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
-
multifunctional protein involved in S-adenosyl-L-methionine-dependent methylation, pyridine dinucleotide dependent dehydrogenation, and ferrochelation, second of three steps leading to formation of siroheme from uroporphyrinogen III
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
-
multifunctional protein involved in S-adenosyl-L-methionine-dependent methylation, pyridine dinucleotide dependent dehydrogenation, and ferrochelation, second of three steps leading to formation of siroheme from uroporphyrinogen III
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
unlike Met8p and CysG, SirC has no chelatase activity
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
siroheme and cobalamin biosynthesis, second of three steps leading to formation of siroheme from uroporphyrinogen III
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
Priestia megaterium DSM 509
unlike Met8p and CysG, SirC has no chelatase activity
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
Priestia megaterium DSM 509
siroheme and cobalamin biosynthesis, second of three steps leading to formation of siroheme from uroporphyrinogen III
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
second of three steps leading to formation of siroheme from uroporphyrinogen III
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
bifunctional dehydrogenase and ferrochelatase, second of three steps leading to formation of siroheme from uroporphyrinogen III
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
-
siroheme and cobalamin biosynthesis, second of three steps leading to formation of siroheme from uroporphyrinogen III
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
-
tetrapyrrole and cobalamin biosynthesis, second of three steps leading to formation of siroheme from uroporphyrinogen III
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
-
-
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
-
-
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
-
precorrin-2 is the precursor of both siroheme and B12, first reaction specific to B12 synthesis, second of three steps leading to formation of siroheme from uroporphyrinogen III
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
-
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
sirohydrochlorin + Fe2+
siroheme + H+
-
-
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
-
multifunctional protein involved in S-adenosyl-L-methionine-dependent methylation, pyridine dinucleotide dependent dehydrogenation, and ferrochelation, second of three steps leading to formation of siroheme from uroporphyrinogen III
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
-
multifunctional protein involved in S-adenosyl-L-methionine-dependent methylation, pyridine dinucleotide dependent dehydrogenation, and ferrochelation, second of three steps leading to formation of siroheme from uroporphyrinogen III
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
siroheme and cobalamin biosynthesis, second of three steps leading to formation of siroheme from uroporphyrinogen III
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
Priestia megaterium DSM 509
siroheme and cobalamin biosynthesis, second of three steps leading to formation of siroheme from uroporphyrinogen III
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
second of three steps leading to formation of siroheme from uroporphyrinogen III
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
bifunctional dehydrogenase and ferrochelatase, second of three steps leading to formation of siroheme from uroporphyrinogen III
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
-
siroheme and cobalamin biosynthesis, second of three steps leading to formation of siroheme from uroporphyrinogen III
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
-
tetrapyrrole and cobalamin biosynthesis, second of three steps leading to formation of siroheme from uroporphyrinogen III
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
-
-
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
-
precorrin-2 is the precursor of both siroheme and B12, first reaction specific to B12 synthesis, second of three steps leading to formation of siroheme from uroporphyrinogen III
-
?
precorrin-2 + NAD+
sirohydrochlorin + NADH + H+
-
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
-
enzyme catalyzes cobalt insertion leading to B12 synthesis
Fe2+
-
enzyme catalyzes iron insertion leading to siroheme synthesis
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
formerly Rhizobium leguminosarum biovar phaseoli, wild-type strain CE3, mutant strain CTNUX8
SwissProt
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Show AA Sequence and Transmembrane Helices (20904 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homodimer
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
orthorhombic space group P2(1)2(1)2(1), unit cell dimensions a = 60.73 A, b = 121.49 A, c = 130.79 A
-
S128A mutant enzyme bound to precorrin-2, sirohydrochlorin, and a cobalt-sirohydrochlorin product, hanging drop vapor diffusion method, using 100 mM MES pH 5.0, 500 mM NaCl, 1% (v/v) 2-mercaptoethanol and 10-20% (w/v) PEG4000
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S128A
the variant is more active for dehydrogenation and chelation than wild type enzyme
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli LMG194 cells
MET8 mutants complemented by Salmonella typhimurium cysG, cloned and expressed in Escherichia coli
-
sequenced and overproduced, sirABC gene cluster complements Escherichia coli cysG mutants
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Raux, E.; McVeigh, T.; Peters, S.E.; Leustek, T.; Warren, M.J.
The role of Saccharomyces cerevisiae MET1p and MET8p in sirohaem and cobalamin biosynthesis
Biochem. J.
338
701-708
1999
Saccharomyces cerevisiae
-
brenda
Warren, M.J.; Raux, E.; Schubert, H.L.; Escalante-Semerena, J.C.
The biosynthesis of adenosylcobalamin (vitamin B12)
Nat. Prod. Rep.
19
390-412
2002
Saccharomyces cerevisiae
brenda
Schubert, H.L.; Raux, E.; Brindley, A.A.; Leech, H.K.; Wilson, K.S.; Hill, C.P.; Warren, M.J.
The structure of Saccharomyces cerevisiae Met8p, a bifunctional dehydrogenase and ferrochelatase
EMBO J.
21
2068-2075
2002
Saccharomyces cerevisiae (P15807), Saccharomyces cerevisiae
brenda
Warren, M.J.; Bolt, E.L.; Roessner, C.A.; Scott, A.I.; Spencer, J.B.; Woodcock, S.C.
Gene dissection demonstrates that the Escherichia coli cysG gene encodes a multifunctional protein
Biochem. J.
302
837-844
1994
Escherichia coli, Escherichia coli CR252
-
brenda
Raux, E.; Leech, H.K.; Beck, R.; Schubert, H.L.; Santander, P.J.; Roessner, C.A.; Scott, A.I.; Martens, J.H.; Jahn, D.; Thermes, C.; Rambach, A.; Warren, M.J.
Identification and functional analysis of enzymes required for precorrin-2 dehydrogenation and metal ion insertion in the biosynthesis of sirohaem and cobalamin in Bacillus megaterium
Biochem. J.
370
505-516
2003
Priestia megaterium (P61818), Priestia megaterium, Priestia megaterium DSM 509 (P61818)
brenda
Fazzio, T.G.; Roth, J.R.
Evidence that the CysG protein catalyzes the first reaction specific to B12 synthesis in Salmonella typhimurium, insertion of cobalt
J. Bacteriol.
178
6952-6959
1996
Salmonella enterica subsp. enterica serovar Typhimurium
brenda
Tate, R.; Riccio, A.; Iaccarino, M.; Patriarca, E.J.
A cysG mutant strain of Rhizobium etli pleiotropically defective in sulfate and nitrate assimilation
J. Bacteriol.
179
7343-7350
1997
Rhizobium etli (O50477)
brenda
Stroupe, M.E.; Leech, H.K.; Daniels, D.S.; Warren, M.J.; Getzoff, E.D.
CysG structure reveals tetrapyrrole-binding features and novel regulation of siroheme biosynthesis
Nat. Struct. Biol.
10
1064-1073
2003
Salmonella enterica
brenda
Schubert, H.L.; Rose, R.S.; Leech, H.K.; Brindley, A.A.; Hill, C.P.; Rigby, S.E.; Warren, M.J.
Structure and function of SirC from Bacillus megaterium - a metal binding precorrin-2 dehydrogenase
Biochem. J.
415
257-263
2008
Priestia megaterium (P61818), Priestia megaterium
brenda
Videira, M.A.M.; Lobo, S.A.L.; Sousa, F.L.; Saraiva, L.M.
Identification of the sirohaem biosynthesis pathway in Staphylococcus aureus
FEBS J.
287
1537-1553
2020
Staphylococcus aureus (A0A0H3KAM1), Staphylococcus aureus Newman (A0A0H3KAM1)
brenda