Nicotinate-nucleotide–dimethylbenzimidazole phosphoribosyltransferase (CobT)

Nicotinate-nucleotide–dimethylbenzimidazole phosphoribosyltransferase, commonly referred to as CobT, is an essential enzyme involved in the biosynthesis of cobalamin (Vitamin B12) in various microorganisms [UniProt: P29963]. It specifically catalyzes the transfer of a phosphoribosyl group from nicotinate mononucleotide to 5,6-dimethylbenzimidazole, producing alpha-ribazole-5'-phosphate and nicotinate [PMID: 11297419]. This reaction is a critical step in the assembly of the lower ligand of the cobalamin molecule, which is necessary for the function of enzymes involved in DNA synthesis and amino acid metabolism [PMID: 7525977]. Since humans lack the metabolic pathway for de novo Vitamin B12 synthesis and must acquire the vitamin through their diet, CobT is considered a potential target for the development of selective antimicrobial agents [PMID: 11297419]. Inhibiting CobT disrupts the production of cobamides, which are vital cofactors for bacterial survival and pathogenesis [PMID: 10411888]. Research into CobT inhibitors focuses on exploiting the enzyme's unique ability to form alpha-glycosidic linkages, a feature rarely seen in eukaryotic phosphoribosyltransferases, which typically form beta-linkages [PMID: 11297419]. While no clinical drugs currently target CobT, it remains a subject of interest for narrow-spectrum antibiotic development [PMID: 11297419].

Other names

CobTDimethylbenzimidazole phosphoribosyltransferaseNaMN:DBI phosphoribosyltransferaseNicotinate-nucleotide:dimethylbenzimidazole phosphoribosyltransferase

Inhibition of the phosphoribosyltransferase activity to prevent the formation of alpha-ribazole-5'-phosphate, thereby blocking the synthesis of Vitamin B12 (cobalamin) in bacteria [PMID: 11297419].