Disease relevance of cobT

• We report the purification and biochemical characterization of the cobalamin biosynthetic enzyme nicotinate-mononucleotide:5, 6-dimethylbenzimidazole phosphoribosyltransferase (CobT) from Salmonella typhimurium. cobT was overexpressed and the protein purified to approximately 97% homogeneity [1].

High impact information on cobT

• CobB, a new member of the SIR2 family of eucaryotic regulatory proteins, is required to compensate for the lack of nicotinate mononucleotide:5,6-dimethylbenzimidazole phosphoribosyltransferase activity in cobT mutants during cobalamin biosynthesis in Salmonella typhimurium LT2 [2].
• NH2-terminal sequence analysis confirmed that the protein encoded by cobT was purified [1].
• Strains with a MudJr insertion in the cobT gene at the 5' end of the cob operon plus a Tn10dGn insertion positioned either clockwise or counterclockwise from cobT were exposed to a burst of RES protein [3].
• Farther counterclockwise, a serine tRNA gene (serU or supD) is weakly cotransducible with the cobT gene [4].
• Some cobT mutants appear defective only in DMB synthesis, since they grow on low levels of DMB and retain their CobII phenotype in the presence of a cobB mutation [4].

Biological context of cobT

• The cobT gene is the last gene in the operon [4].
• Thus, the phenotype of Salmonella cobT mutants conflicts with the reported activity of the affected enzyme, while Pseudomonas mutants have the expected phenotype [4].
• Four CobII (DMB-) mutations mapping to different deletion intervals of the CobII region were sequenced; all affect the cobT open reading frame [4].

Associations of cobT with chemical compounds

• The end of the cob operon: evidence that the last gene (cobT) catalyzes synthesis of the lower ligand of vitamin B12, dimethylbenzimidazole [4].

References