1d0s

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spinqualitylabelsall models 1d0s, resolution 1.9Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF NICOTINATE MONONUCLEOTIDE : 5,6-DIMETHYLBENZIMIDAZOLE PHOSPHORIBOSYLTRANSFERASE (COBT) FROM SALMONELLA TYPHIMURIUM COMPLEXED WITH 5, 6-DIMETHYLBENZIMIDAZOLE

Overview

Nicotinate mononucleotide:5,6-dimethylbenzimidazole, phosphoribosyltransferase (CobT) from Salmonella typhimurium plays a, central role in the synthesis of alpha-ribazole, which is a key component, of the lower ligand of cobalamin. Two X-ray structures of CobT are, reported here at 1.9 A resolution. First, a complex of CobT with, 5,6-dimethylbenzimidazole, and second, a complex of CobT with its reaction, products, nicotinate and alpha-ribazole-5'-phosphate. CobT was, cocrystallized with 5,6-dimethylbenzimidazole (DMB) in the space group, P2(1)2(1)2 with unit cell dimensions of a = 72.1 A, b = 90.2 A, and c =, 47.5 A and one protomer per asymmetric unit. Subsequently, the crystals, containing DMB were soaked in nicotinate mononucleotide whereupon the, physiological reaction occurred in the crystal lattice to yield nicotinate, and alpha-ribazole-5'-phosphate. These studies show that CobT is a dimer, where each subunit consists of two domains. The large domain is dominated, by a parallel six-stranded beta-sheet with connecting alpha-helices that, exhibit the topology of a Rossmann fold. The small domain is made from, components of the N- and C-terminal sections of the polypeptide chain and, contains a three-helix bundle. The fold of CobT is unrelated to the type I, and II phosphoribosylpyrophosphate dependent transferases and does not, appear to be related to any other protein whose structure is known. The, enzyme active site is located in a large cavity formed by the loops at the, C-terminal ends of the beta-strands and the small domain of the, neighboring subunit. DMB binds in a hydrophobic pocket created in part by, the neighboring small domain. This is consistent with the broad, specificity of this enzyme for aromatic substrates [Trzebiatowski, J. R., Escalante-Semerena (1997) J. Biol. Chem. 272, 17662-17667]. The binding, site for DMB suggests that Glu317 is the catalytic base required for the, reaction. The remainder of the cavity binds the nicotinate and, ribose-5'-phosphate moieties, which are nestled within the loops at the, ends of the beta-strands. Interestingly, the orientation of the substrate, and products are opposite from that expected for a Rossmann fold.

About this Structure

1D0S is a Single protein structure of sequence from Salmonella typhimurium with PO4 and DMD as ligands. Active as Nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase, with EC number 2.4.2.21 Full crystallographic information is available from OCA.

Reference

The three-dimensional structures of nicotinate mononucleotide:5,6- dimethylbenzimidazole phosphoribosyltransferase (CobT) from Salmonella typhimurium complexed with 5,6-dimethybenzimidazole and its reaction products determined to 1.9 A resolution., Cheong CG, Escalante-Semerena JC, Rayment I, Biochemistry. 1999 Dec 7;38(49):16125-35. PMID:10587435

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