InterPro domain: IPR011629

General Information

  • Identifier IPR011629
  • Description Cobalamin (vitamin B12) biosynthesis CobW-like, C-terminal
  • Number of genes 363
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Abstract

Cobalamin (vitamin B12) is a structurally complex cofactor, consisting of a modified tetrapyrrole with a centrally chelated cobalt. Cobalamin is usually found in one of two biologically active forms: methylcobalamin and adocobalamin. Most prokaryotes, as well as animals, have cobalamin-dependent enzymes, whereas plants and fungi do not appear to use it. In bacteria and archaea, these include methionine synthase, ribonucleotide reductase, glutamate and methylmalonyl-CoA mutases, ethanolamine ammonia lyase, and diol dehydratase [ 1 ]. In mammals, cobalamin is obtained through the diet, and is required for methionine synthase and methylmalonyl-CoA mutase [ 2 ].

There are at least two distinct cobalamin biosynthetic pathways in bacteria [ 3 ]:

  • Aerobic pathway that requires oxygen and in which cobalt is inserted late in the pathway [ 4 ]; found in Pseudomonas denitrificans and Rhodobacter capsulatus.
  • Anaerobic pathway in which cobalt insertion is the first committed step towards cobalamin synthesis [ 5 , 6 ]; found in Salmonella typhimurium, Bacillus megaterium, and Propionibacterium freudenreichii subsp. shermanii.

Either pathway can be divided into two parts: (1) corrin ring synthesis (differs in aerobic and anaerobic pathways) and (2) adenosylation of corrin ring, attachment of aminopropanol arm, and assembly of the nucleotide loop (common to both pathways) [ 7 ]. There are about 30 enzymes involved in either pathway, where those involved in the aerobic pathway are prefixed Cob and those of the anaerobic pathway Cbi. Several of these enzymes are pathway-specific: CbiD, CbiG, and CbiK are specific to the anaerobic route of S. typhimurium, whereas CobE, CobF, CobG, CobN, CobS, CobT, and CobW are unique to the aerobic pathway of P. denitrificans.

CobW proteins are generally found proximal to the trimeric cobaltochelatase subunit CobN, which is essential for vitamin B12 (cobalamin) biosynthesis [ 8 , 8 ]. They contain a P-loop nucleotide-binding loop in the N-terminal domain and a histidine-rich region in the C-terminal portion suggesting a role in metal binding, possibly as an intermediary between the cobalt transport and chelation systems. CobW might be involved in cobalt reduction leading to cobalt(I) corrinoids.

This entry represents the C-terminal domain found in CobW, as well as in P47K ( P31521 ), a Pseudomonas chlororaphis protein needed for nitrile hydratase expression [ 9 ].


1. Comparative genomics of the vitamin B12 metabolism and regulation in prokaryotes. J. Biol. Chem. 278, 41148-59
2. B12 trafficking in mammals: A for coenzyme escort service. ACS Chem. Biol. 1, 149-59
3. Multiple biosynthetic pathways for vitamin B12: variations on a central theme. Vitam. Horm. 61, 267-97
4. Aerobic synthesis of vitamin B12: ring contraction and cobalt chelation. Biochem. Soc. Trans. 33, 815-9
5. Isolation and characterization of 14 additional genes specifying the anaerobic biosynthesis of cobalamin (vitamin B12) in Propionibacterium freudenreichii (P. shermanii). Microbiology (Reading, Engl.) 148, 1845-53
6. Elucidation of the anaerobic pathway for the corrin component of cobalamin (vitamin B12). Proc. Natl. Acad. Sci. U.S.A. 110, 14906-11
7. Biosynthesis of cobalamin (vitamin B12): a bacterial conundrum. Cell. Mol. Life Sci. 57, 1880-93
8. Metal binding properties of Escherichia coli YjiA, a member of the metal homeostasis-associated COG0523 family of GTPases. Biochemistry 52, 1788-1801
9. Nitrile hydratase gene from Rhodococcus sp. N-774 requirement for its downstream region for efficient expression. Biosci. Biotechnol. Biochem. 58, 1859-65

Species distribution

Gene table

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