1JHM

Three-dimensional Structure of CobT in Complex with 5-methylbenzimidazole

1JHM の概要

• エントリーDOI: 10.2210/pdb1jhm/pdb
• 関連するPDBエントリー: 1D0S 1D0V 1JH8 1JHA 1JHO 1JHP 1JHQ 1JHR 1JHU 1JHV 1JHX 1JHY
• 分子名称: Nicotinate Mononucleotide:5,6-Dimethylbenzimidazole Phosphoribosyltransferase, PHOSPHATE ION, 5-METHYLBENZIMIDAZOLE, ... (4 entities in total)
• 機能のキーワード: cobt, cobalamin biosynthesis, lower ligand, cobamides, nn:dbi prt, n1-alpha-phosphoribosyltransferase, transferase
• 由来する生物種: Salmonella enterica
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36997.70

構造登録者

Cheong, C.G.,Escalante-Semerena, J.,Rayment, I. (登録日: 2001-06-28, 公開日: 2001-10-18, 最終更新日: 2024-10-30)

主引用文献

Cheong, C.G.,Escalante-Semerena, J.C.,Rayment, I.
Structural investigation of the biosynthesis of alternative lower ligands for cobamides by nicotinate mononucleotide: 5,6-dimethylbenzimidazole phosphoribosyltransferase from Salmonella enterica.
J.Biol.Chem., 276:37612-37620, 2001

PubMed Abstract: 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.

PubMed: 11441022
DOI: 10.1074/jbc.M105390200

実験手法

X-RAY DIFFRACTION (2.2 Å)