Alpha-5,6-dimethylbenzimidazole adenine dinucleotide (alpha-DAD), a putative new intermediate of coenzyme B12 biosynthesis in Salmonella typhimurium.

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Maggio-Hall LA, Escalante-Semerena JC

Alpha-5,6-dimethylbenzimidazole adenine dinucleotide (alpha-DAD), a putative new intermediate of coenzyme B12 biosynthesis in Salmonella typhimurium.

Microbiology. 2003 Apr;149(Pt 4):983-90.

PubMed ID

12686640 [ View in PubMed

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Abstract

The CobT enzyme of Salmonella typhimurium was shown in vitro to have NAD(+)-dependent ADPribosyltransferase activity. The CobT enzyme transferred the ADPribosyl moiety of NAD(+) onto 5,6-dimethylbenzimidazole (DMB) yielding a new dinucleotide, namely alpha-5,6-dimethylbenzimidazole adenine dinucleotide (alpha-DAD), whose identity was established by mass spectrometry. The N(1)-(alpha-D-ribosyl)-5,6-dimethylbenzimidazoyl moiety (alpha-ribazole) of alpha-DAD was incorporated into adenosylcobalamin (AdoCbl) by cell-free extracts of S. typhimurium, indicating that alpha-DAD served as an intermediate of AdoCbl biosynthesis. The rate of transfer of the ADPribosyl moiety was slower than the rate of transfer of the phosphoribosyl moiety of nicotinate mononucleotide (NaMN) to DMB. The CobT enzyme displayed a low K(m) for NaMN (0.51 mM) relative to the one for NAD(+) (9 mM); nicotinate adenine dinucleotide (NaAD) and nicotinamide mononucleotide (NMN) also served as substrates for CobT. In spite of the high K(m) of CobT for NAD(+), the latter is proposed to be a relevant physiological substrate of CobT, given that the intracellular concentrations of NaMN, NMN and NaAD in actively growing S. typhimurium are undetectable. Evidence shows that extracts of S. typhimurium contain an as-yet unidentified dinucleotide pyrophosphatase that can cleave alpha-DAD into alpha-ribazole-5'-P and AMP; alpha-ribazole-5'-P can then enter the AdoCbl biosynthetic pathway.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Adenine	Nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase	Protein	Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)	Unknown	Not Available	Details