D-Ala-D-Ala ligases from glycopeptide antibiotic-producing organisms are highly homologous to the enterococcal vancomycin-resistance ligases VanA and VanB
D-Ala-D-Ala ligases from glycopeptide antibiotic-producing organisms are highly homologous to the enterococcal vancomycin-resistance ligases VanA and VanB
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DOI：
10.1073/pnas.94.12.6480
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发表时间：
1997-06-10
影响因子：
11.1
通讯作者：
Wright, GD
中科院分区：
文献类型：
--
作者：
Marshall, CG;Broadhead, G;Wright, GD
抗生素耐药性危机导致人们越来越担心无法治疗的微生物的出现，肠球菌对糖肽类抗生素万古霉素的耐药性，以及这些病原体在整个环境中的传播，表明这种情况是事实而不是虚构。万古霉素耐药性的基础是缩肽 D-丙氨酸-D-乳酸的制造， 被掺入肽聚糖细胞壁中，代替万古霉素靶标 D-Ala-D-Ala。耐药机制的关键是能够形成酯的 D-Ala-D-Ala 连接酶的产生，从万古霉素耐药肠球菌中克隆了两种高效的缩酚肽连接酶：VanA 和 VanB，这些连接酶彼此显示出很高的氨基酸序列相似性（约 75%），但与其他 D-Ala-D-X 连接酶（60%）相比较低，但不是 与其他 D-Ala-D-X 连接酶（
The crisis in antibiotic resistance has resulted in an increasing fear of the emergence of untreatable organisms, Resistance to the glycopeptide antibiotic vancomycin in the enterococci, and the spread of these pathogens throughout the environment, has shown that this scenario is a matter of fact rather than fiction, The basis for vancomycin resistance is the manufacture of the depsipeptide D-Ala-D-lactate, which is incorporated into the peptidoglycan cell wall in place of the vancomycin target D-Ala-D-Ala. Pivotal to the resistance mechanism is the production of a D-Ala-D-Ala ligase capable of ester formation, Two highly efficient depsipeptide ligases have been cloned from vancomycin-resistant enterococci: VanA and VanB, These ligases show high amino acid sequence similarity to each other (approximate to 75%), but less so to other D-Ala-D-X ligases (60%) but not to other D-Ala-D-X ligases (