CATH Classification

Domain Context

CATH Clusters

Superfamily Siroheme synthase; domain 2
Functional Family Siroheme biosynthesis protein MET8

Enzyme Information

4.99.1.4
Sirohydrochlorin ferrochelatase.
based on mapping to UniProt P15807
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.
1.3.1.76
Precorrin-2 dehydrogenase.
based on mapping to UniProt P15807
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.

UniProtKB Entries (1)

P15807
MET8_YEAST
Saccharomyces cerevisiae S288C
Siroheme biosynthesis protein MET8

PDB Structure

PDB 1KYQ
External Links
Method X-RAY DIFFRACTION
Organism Escherichia
Primary Citation
The structure of Saccharomyces cerevisiae Met8p, a bifunctional dehydrogenase and ferrochelatase.
Schubert, H.L., Raux, E., Brindley, A.A., Leech, H.K., Wilson, K.S., Hill, C.P., Warren, M.J.
EMBO J.