Reaction: 2 S-adenosyl-L-methionine + uroporphyrinogen III = 2 S-adenosyl-L-homocysteine + precorrin-2 (overall reaction)
(1a) S-adenosyl-L-methionine + uroporphyrinogen III = S-adenosyl-L-homocysteine + precorrin-1
(1b) S-adenosyl-L-methionine + precorrin-1 = S-adenosyl-L-homocysteine + precorrin-2
For diagram click here.
Glossary: uroprphyrinogen-III = 5,10,15,20,22,24-hexahydrouroporphyrin-III
Other name(s): uroporphyrinogen methyltransferase; uroporphyrinogen-III methyltransferase; adenosylmethionine-uroporphyrinogen III methyltransferase; S-adenosyl-L-methionine-dependent uroporphyrinogen III methylase; uroporphyrinogen-III methylase; SirA; CysG; CobA [ambiguous see EC 22.214.171.124]; SUMT; uroporphyrin-III C-methyltransferase (incorrect); S-adenosyl-L-methionine:uroporphyrin-III C-methyltransferase (incorrect)
Systematic name: S-adenosyl-L-methionine:uroporphyrinogen-III C-methyltransferase
Comments: This enzyme catalyses 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 126.96.36.199, precorrin-2 dehydrogenase) and the third step involves the chelation of Fe2+ to sirohydrochlorin to form siroheme (EC 188.8.131.52, 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 SirA being responsible for the above reaction. Also involved in the biosynthesis of cobalamin.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 125752-76-3
1. Warren, M.J., Gonzalez, M.D., Williams, H.J., Stolowich, N.J. and Scott, A.I. Uroporphyrinogen-III methylase catalyzes the enzymatic-synthesis of sirohydrochlorin-II and sirohydrochlorin-IV by a clockwise mechanism. J. Am. Chem. Soc. 112 (1990) 5343-5345.
2. Warren, M.J., Roessner, C.A., Santander, P.J. and Scott, A.I. The Escherichia coli cysG gene encodes S-adenosylmethionine-dependent uroporphyrinogen III methylase. Biochem. J. 265 (1990) 725-729. [PMID: 2407234]
3. Schubert, H.L., Raux, E., Brindley, A.A., Leech, H.K., Wilson, K.S., Hill, C.P. and Warren, M.J. The structure of Saccharomyces cerevisiae Met8p, a bifunctional dehydrogenase and ferrochelatase. EMBO J. 21 (2002) 2068-2075. [PMID: 11980703]