CATH Classification

Domain Context

CATH Clusters

Superfamily NAD(P)-binding Rossmann-like Domain
Functional Family Siroheme synthase

Enzyme Information

1.3.1.76
Precorrin-2 dehydrogenase.
based on mapping to UniProt P25924
Precorrin-2 + NAD(+) = sirohydrochlorin + NADH.
-!- Catalyzes 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) and the third step involves the chelation of ferrous iron to sirohydrochlorin to form siroheme (EC 4.99.1.4). -!- In Saccharomyces cerevisiae, the last two steps are carried out by a single bifunctional enzyme, Met8p. -!- In some bacteria, steps 1-3 are catalyzed 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.
2.1.1.107
Uroporphyrinogen-III C-methyltransferase.
based on mapping to UniProt P25924
2 S-adenosyl-L-methionine + uroporphyrinogen III = 2 S-adenosyl-L- homocysteine + precorrin-2.
-!- This enzyme catalyzes two sequential methylation reactions, the first forming precorrin-1 and the second leading to the formation of precorrin-2. -!- It is the first of three steps leading to the formation of siroheme from uroporphyrinogen III. -!- The second step involves an NAD(+)-dependent dehydrogenation to form sirohydrochlorin from precorrin-2 (EC 1.3.1.76) and the third step involves the chelation of Fe(2+) to sirohydrochlorin to form siroheme (EC 4.99.1.4). -!- In Saccharomyces cerevisiae, the last two steps are carried out by a single bifunctional enzyme, Met8p. -!- In some bacteria, steps 1-3 are catalyzed by a single multifunctional protein called CysG, whereas in Bacillus megaterium, three separate enzymes carry out each of the steps, with SirA being responsible for the above reaction. -!- Also involved in the biosynthesis of cobalamin.
4.99.1.4
Sirohydrochlorin ferrochelatase.
based on mapping to UniProt P25924
Siroheme + 2 H(+) = sirohydrochlorin + Fe(2+).
-!- This enzyme catalyzes the third 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) and the second step involves an NAD(+)-dependent dehydrogenation to form sirohydrochlorin from precorrin-2 (EC 1.3.1.76). -!- In Saccharomyces cerevisiae, the last two steps are carried out by a single bifunctional enzyme, Met8p. -!- In some bacteria, steps 1-3 are catalyzed by a single multifunctional protein called CysG, whereas in Bacillus megaterium, three separate enzymes carry out each of the steps, with SirB being responsible for the above reaction.

UniProtKB Entries (1)

P25924
CYSG_SALTY
Salmonella enterica subsp. enterica serovar Typhimurium str. LT2
Siroheme synthase

PDB Structure

PDB 1PJT
External Links
Method X-RAY DIFFRACTION
Organism Escherichia
Primary Citation
CysG structure reveals tetrapyrrole-binding features and novel regulation of siroheme biosynthesis.
Stroupe, M.E., Leech, H.K., Daniels, D.S., Warren, M.J., Getzoff, E.D.
Nat.Struct.Biol.