1QD8

COMPLEX OF VANCOMYCIN WITH N-ACETYL GLYCINE

1QD8 の概要

• エントリーDOI: 10.2210/pdb1qd8/pdb
• 関連するPDBエントリー: 1AA5 1C0Q 1C0R 1FVM 1GAC 1GHG 1PN3 1PNV 1RRV 1SHO
• 関連するBIRD辞書のPRD_ID: PRD_000204
• 分子名称: VANCOMYCIN, vancosamine-(1-2)-beta-D-glucopyranose, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: 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: 3170.10

構造登録者

Loll, P.J.,Kaplan, J.,Selinsky, B.,Axelsen, P.H. (登録日: 1999-07-15, 公開日: 1999-08-16, 最終更新日: 2023-12-27)

主引用文献

Loll, P.J.,Kaplan, J.,Selinsky, B.S.,Axelsen, P.H.
Vancomycin Binding to Low-Affinity Ligands: Delineating a Minimum Set of Interactions Necessary for High-Affinity Binding.
J.Med.Chem., 42:4714-, 1999

PubMed Abstract: Bacterial resistance to vancomycin has been attributed to the loss of an intermolecular hydrogen bond between vancomycin and its peptidoglycan target when cell wall biosynthesis proceeds via depsipeptide intermediates rather than the usual polypeptide intermediates. To investigate the relative importance of this hydrogen bond to vancomycin binding, we have determined crystal structures at 1.0 A resolution for the vancomycin complexes with three ligands that mimic peptides and depsipeptides found in vancomycin-sensitive and vancomycin-resistant bacteria: N-acetylglycine, D-lactic acid, and 2-acetoxy-D-propanoic acid. These, in conjunction with structures that have been reported previously, indicate higher-affinity ligands elicit a structural change in the drug not seen with these low-affinity ligands. They also enable us to define a minimal set of drug-ligand interactions necessary to confer higher-affinity binding on a ligand. Most importantly, these structures point to factors in addition to the loss of an intermolecular hydrogen bond that must be invoked to explain the weaker affinity of vancomycin for depsipeptide ligands. These factors are important considerations for the design of vancomycin analogues to overcome vancomycin resistance.

PubMed: 10579833
DOI: 10.1021/JM990361T

実験手法

X-RAY DIFFRACTION (1 Å)