2IYA

The crystal structure of macrolide glycosyltransferases: A blueprint for antibiotic engineering

2IYA の概要

• エントリーDOI: 10.2210/pdb2iya/pdb
• 分子名称: OLEANDOMYCIN GLYCOSYLTRANSFERASE, URIDINE-5'-DIPHOSPHATE, (3S,5R,6S,7R,8R,11R,12S,13R,14S,15S)-6-HYDROXY-5,7,8,11,13,15-HEXAMETHYL-4,10-DIOXO-14-{[3,4,6-TRIDEOXY-3-(DIMETHYLAMINO)-BETA-D-XYLO-HEXOPYRANOSYL]OXY}-1,9-DIOXASPIRO[2.13]HEXADEC-12-YL 2,6-DIDEOXY-3-O-METHYL-ALPHA-L-ARABINO-HEXOPYRANOSIDE, ... (4 entities in total)
• 機能のキーワード: carbohydrate, glycosylation, glycosyltransferase, enzyme, macrolide, transferase
• 由来する生物種: STREPTOMYCES ANTIBIOTICUS
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 93609.76

構造登録者

Bolam, D.N.,Roberts, S.M.,Proctor, M.R.,Turkenburg, J.P.,Dodson, E.J.,Martinez-Fleites, C.,Yang, M.,Davis, B.G.,Davies, G.J.,Gilbert, H.J. (登録日: 2006-07-13, 公開日: 2007-03-27, 最終更新日: 2024-05-08)

主引用文献

Bolam, D.N.,Roberts, S.M.,Proctor, M.R.,Turkenburg, J.P.,Dodson, E.J.,Martinez-Fleites, C.,Yang, M.,Davis, B.G.,Davies, G.J.,Gilbert, H.J.
The Crystal Structure of Two Macrolide Glycosyltransferases Provides a Blueprint for Host Cell Antibiotic Immunity.
Proc.Natl.Acad.Sci.USA, 104:5336-, 2007

PubMed Abstract: Glycosylation of macrolide antibiotics confers host cell immunity from endogenous and exogenous agents. The Streptomyces antibioticus glycosyltransferases, OleI and OleD, glycosylate and inactivate oleandomycin and diverse macrolides including erythromycin, respectively. The structure of these enzyme-ligand complexes, in tandem with kinetic analysis of site-directed variants, provide insight into the interaction of macrolides with their synthetic apparatus. Erythromycin binds to OleD and the 23S RNA of its target ribosome in the same conformation and, although the antibiotic contains a large number of polar groups, its interaction with these macromolecules is primarily through hydrophobic contacts. Erythromycin and oleandomycin, when bound to OleD and OleI, respectively, adopt different conformations, reflecting a subtle effect on sugar positioning by virtue of a single change in the macrolide backbone. The data reported here provide structural insight into the mechanism of resistance to both endogenous and exogenous antibiotics, and will provide a platform for the future redesign of these catalysts for antibiotic remodelling.

PubMed: 17376874
DOI: 10.1073/PNAS.0607897104

実験手法

X-RAY DIFFRACTION (1.7 Å)