1jhr
Three-dimensional Structure of CobT in Complex with Reaction Products of 2-hydroxypurine and NaMN
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OverviewOverview
Nicotinate mononucleotide (NaMN):5,6-dimethylbenzimidazole, phosphoribosyltransferase (CobT) from Salmonella enterica plays a central, role in the synthesis of alpha-ribazole, a key component of the lower, ligand of cobalamin. Surprisingly, CobT can phosphoribosylate a wide range, of aromatic substrates, giving rise to a wide variety of lower ligands in, cobamides. To understand the molecular basis for this lack of substrate, specificity, the x-ray structures of CobT complexed with adenine, 5-methylbenzimidazole, 5-methoxybenzimidazole, p-cresol, and phenol were, determined. Furthermore, adenine, 5-methylbenzimidazole, 5-methoxybenzimidazole, and 2-hydroxypurine were observed to react with, NaMN within the crystal lattice and undergo the phosphoribosyl transfer, reaction to form product. Significantly, the stereochemistries of all, products are identical to those found in vivo. Interestingly, p-cresol and, phenol, which are the lower ligand in Sporomusa ovata, bound to CobT but, did not react with NaMN. This study provides a structural explanation for, how CobT can phosphoribosylate most of the commonly observed lower ligands, found in cobamides with the exception of the phenolic lower ligands, observed in S. ovata. This is accomplished with minor conformational, changes in the side chains that constitute the 5,6-dimethylbenzimidazole, binding site. These investigations are consistent with the implication, that the nature of the lower ligand is controlled by metabolic factors, rather by the specificity of the phosphoribosyltransferase.
About this StructureAbout this Structure
1JHR is a Single protein structure of sequence from Salmonella enterica with NIO and P2P as ligands. Active as Nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase, with EC number 2.4.2.21 Full crystallographic information is available from OCA.
ReferenceReference
Structural investigation of the biosynthesis of alternative lower ligands for cobamides by nicotinate mononucleotide: 5,6-dimethylbenzimidazole phosphoribosyltransferase from Salmonella enterica., Cheong CG, Escalante-Semerena JC, Rayment I, J Biol Chem. 2001 Oct 5;276(40):37612-20. Epub 2001 Jul 5. PMID:11441022
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