5M2K

Crystal structure of vancomycin-Zn(II) complex

5M2K の概要

• エントリーDOI: 10.2210/pdb5m2k/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000204
• 分子名称: vancomycin, vancosamine-(1-2)-beta-D-glucopyranose, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: vancomycin, zinc, glycopeptide, antibiotic
• 由来する生物種: Amycolatopsis orientalis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 3136.18

構造登録者

Zarkan, A.,Macklyne, H.-R.,Chirgadze, D.Y.,Bond, A.D.,Hesketh, A.R.,Hong, H.-J. (登録日: 2016-10-13, 公開日: 2017-07-19, 最終更新日: 2025-04-09)

主引用文献

Zarkan, A.,Macklyne, H.R.,Chirgadze, D.Y.,Bond, A.D.,Hesketh, A.R.,Hong, H.J.
Zn(II) mediates vancomycin polymerization and potentiates its antibiotic activity against resistant bacteria.
Sci Rep, 7:4893-4893, 2017

PubMed Abstract: Vancomycin is known to bind to Zn(II) and can induce a zinc starvation response in bacteria. Here we identify a novel polymerization of vancomycin dimers by structural analysis of vancomycin-Zn(II) crystals and fibre X-ray diffraction. Bioassays indicate that this structure is associated with an increased antibiotic activity against bacterial strains possessing high level vancomycin resistance mediated by the reprogramming of peptidoglycan biosynthesis to use precursors terminating in D-Ala-D-Lac in place of D-Ala-D-Ala. Polymerization occurs via interaction of Zn(II) with the N-terminal methylleucine group of vancomycin, and we show that the activity of other glycopeptide antibiotics with this feature can also be similarly augmented by Zn(II). Construction and analysis of a model strain predominantly using D-Ala-D-Lac precursors for peptidoglycan biosynthesis during normal growth supports the hypothesis that Zn(II) mediated vancomycin polymerization enhances the binding affinity towards these precursors.

PubMed: 28687742
DOI: 10.1038/s41598-017-04868-2

実験手法

X-RAY DIFFRACTION (1 Å)