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Cobalamins (vitamin B12), both as deoxyadenosylcobalamin and methylcobalamin, are involved as cofactors in a variety of enzymatic reactions and are synthesized by some bacteria and archaea. About thirty enzymes are required to manufacture cobalamins, some of the most complex nonpolymeric molecules biosynthesized in the cell. Cobalamin biosynthesis can be divided into three distinct sections. The first results in the synthesis of the corrin ring component, cobinamide, from the ubiquitous tetrapyrrole primogenitor uroporphyrinogen III by a series of reactions including eight S-adenosyl-L-methionine-dependent methylations, ring contraction, cobalt chelation, decarboxylation, amidations, and 1-amino-2-propanol attachment. The second results in the synthesis of the lower axial ligand, dimethylbenzimidazole (DMB) and the third results in the assembly of the final coenzyme from the attachment of the corrin ring to the DMB as well as the addition of the upper coordinating ligand for the cobalt, either an adenosyl or a methyl group [1].

The precorrin-6x reductase (EC 1.3.1.54) domain is found in proteins (cobK and cbiJ), which are involved in part I of the cobalamin biosynthesis pathway. It catalyzes the NADPH-dependent reduction of precorrin-6x to a dihydro derivative named precorrin-6y [2,3].

The profile we developed covers the entire precorrin-6x reductase domain.

August 2004 / First entry.

PROSITE method (with tools and information) covered by this documentation:

COBK_CBIJ, PS51014; Precorrin-6x reductase domain profile  (MATRIX)

Sequences known to belong to this class detected by the profile: ALL Other sequence(s) detected in Swiss-Prot: NONE

• Domain architecture view of Swiss-Prot proteins matching PS51014 • Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS51014 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS51014 • Scan Swiss-Prot/TrEMBL entries against PS51014 • view ligand binding statistics

1	Authors	Raux E., Schubert H.L., Warren M.J.
	Title	Biosynthesis of cobalamin (vitamin B12): a bacterial conundrum.
	Source	Cell. Mol. Life Sci. 57:1880-1893(2000).
	PubMed ID	11215515

2	Authors	Blanche F., Thibaut D., Famechon A., Debussche L., Cameron B., Crouzet J.
	Title	Precorrin-6x reductase from Pseudomonas denitrificans: purification and characterization of the enzyme and identification of the structural gene.
	Source	J. Bacteriol. 174:1036-1042(1992).
	PubMed ID	1732193

3	Authors	Shearer N., Hinsley A.P., Van Spanning R.J.M., Spiro S.
	Title	Anaerobic growth of Paracoccus denitrificans requires cobalamin: characterization of cobK and cobJ genes.
	Source	J. Bacteriol. 181:6907-6913(1999).
	PubMed ID	10559155

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