临床相关肠球菌中万古霉素耐药性的分子基础：D-丙氨酰-D-乳酸连接酶（VanA）的晶体结构
The molecular basis of vancomycin resistance in clinically relevant Enterococci: crystal structure of D-alanyl-D-lactate ligase (VanA).
作者信息
Roper D I, Huyton T, Vagin A, Dodson G
机构信息
York Structural Biology Laboratory, Department of Chemistry, The University of York, Heslington, York YO10 5DD, United Kingdom.
出版信息
Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):8921-5. doi: 10.1073/pnas.150116497.
Abstract
d-alanine-d-lactate ligase from Enterococcus faecium BM4147 is directly responsible for the biosynthesis of alternate cell-wall precursors in bacteria, which are resistant to the glycopeptide antibiotic vancomycin. The crystal structure has been determined with data extending to 2.5-A resolution. This structure shows that the active site has unexpected interactions and is distinct from previous models for d-alanyl-d-lactate ligase mechanistic studies. It appears that the preference of the enzyme for lactate as a ligand over d-alanine could be mediated by electrostatic effects and/or a hydrogen-bonding network, which principally involve His-244. The structure of d-alanyl-d-lactate ligase provides a revised interpretation of the molecular events that lead to vancomycin resistance.
摘要
来自粪肠球菌BM4147的d-丙氨酸-d-乳酸连接酶直接负责细菌中替代细胞壁前体的生物合成，这些细菌对糖肽抗生素万古霉素具有抗性。已通过分辨率高达2.5埃的数据确定了其晶体结构。该结构表明，活性位点具有意想不到的相互作用，与之前用于d-丙氨酰-d-乳酸连接酶机理研究的模型不同。看来，该酶对乳酸作为配体的偏好超过d-丙氨酸，可能是由静电效应和/或氢键网络介导的，其中主要涉及组氨酸-244。d-丙氨酰-d-乳酸连接酶的结构为导致万古霉素抗性的分子事件提供了新的解释。
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