1D0S

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

1D0S の概要

• エントリーDOI: 10.2210/pdb1d0s/pdb
• 関連するPDBエントリー: 1D0V
• 分子名称: NICOTINATE MONONUCLEOTIDE:5,6-DIMETHYLBENZIMIDAZOLE PHOSPHORIBOSYLTRANSFERASE, PHOSPHATE ION, 5,6-DIMETHYLBENZIMIDAZOLE, ... (4 entities in total)
• 機能のキーワード: dinucleotide-binding motif, phosphoribosyl transferase, transferase
• 由来する生物種: Salmonella typhimurium
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36886.73

構造登録者

Cheong, C.-G.,Escalante-Semerena, J.C.,Rayment, I. (登録日: 1999-09-14, 公開日: 1999-12-29, 最終更新日: 2018-01-31)

主引用文献

Cheong, C.G.,Escalante-Semerena, J.C.,Rayment, I.
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.
Biochemistry, 38:16125-16135, 1999

PubMed Abstract: 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.

PubMed: 10587435
DOI: 10.1021/bi991752c

実験手法

X-RAY DIFFRACTION (1.9 Å)