InterPro domain: IPR014776

Tetrapyrroles are large macrocyclic compounds derived from a common biosynthetic pathway [ 1 ]. The end-product, uroporphyrinogen III, is used to synthesise a number of important molecules, including cobalamin (vitamin B12), haem, sirohaem, chlorophyll, coenzyme F430 and phytochromobilin [ 2 ].

This entry represents the C-terminal subdomain 2 from several tetrapyrrole methylases, which consist of two non-similar domains. These enzymes catalyse the methylation of their substrates using S-adenosyl-L-methionine as a methyl source. Enzymes in this family include:

• Uroporphyrinogen III methyltransferase ( 2.1.1.107 ) (SUMT), which catalyses the conversion of uroporphyrinogen III to precorrin-2 at the first branch-point of the tetrapyrrole synthesis pathway, directing the pathway towards cobalamin or sirohaem synthesis [ 3 ].
• Precorrin-2 C20-methyltransferase CobI/CbiL ( 2.1.1.130 ), which introduces a methyl group at C-20 on precorrin-2 to produce precorrin-3A during cobalamin biosynthesis. This reaction is key to the conversion of a porphyrin-type tetrapyrrole ring to a corrin ring [ 4 ]. In some species, this enzyme is part of a bifunctional protein.
• Precorrin-4 C11-methyltransferase CobM/CbiF ( 2.1.1.133 ), which introduces a methyl group at C-11 on precorrin-4 to produce precorrin-5 during cobalamin biosynthesis [ 5 ].
• Sirohaem synthase CysG ( 2.1.1.107 ), domains 4 and 5, which synthesizes sirohaem from uroporphyrinogen III, at the first branch-point in the tetrapyrrole biosynthetic pathway, directing the pathway towards sirohaem synthesis [ 6 ].
• Diphthine synthase ( 2.1.1.98 ), which carries out the methylation step during the modification of a specific histidine residue of elongation factor 2 (EF-2) during diphthine synthesis.

1. Biosynthesis of cobalamin (vitamin B12): a bacterial conundrum. Cell. Mol. Life Sci. 57, 1880-93
2. Tetrapyrrole biosynthesis in higher plants. FEBS J. 58, 321-46
3. Structure/function studies on a S-adenosyl-L-methionine-dependent uroporphyrinogen III C methyltransferase (SUMT), a key regulatory enzyme of tetrapyrrole biosynthesis. J. Mol. Biol. 344, 419-33
4. Crystal structures of CbiL, a methyltransferase involved in anaerobic vitamin B biosynthesis, and CbiL in complex with S-adenosylhomocysteine--implications for the reaction mechanism. null 274, 563-73
5. Genetically engineered synthesis and structural characterization of cobalt-precorrin 5A and -5B, two new intermediates on the anaerobic pathway to vitamin B12: definition of the roles of the CbiF and CbiG enzymes. J. Am. Chem. Soc. 128, 9971-8
6. CysG structure reveals tetrapyrrole-binding features and novel regulation of siroheme biosynthesis. Nat. Struct. Biol. 10, 1064-73