Transpeptidase-mediated incorporation of D-amino acids into bacterial peptidoglycan.

Transpeptidase-mediated incorporation of D-amino acids into bacterial peptidoglycan.
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转肽酶介导的 D-氨基酸掺入细菌肽聚糖。

DOI:
10.1021/ja2040656
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发表时间:
2011-07-20
影响因子:
15
通讯作者:
Kahne, Daniel
Kahne, Daniel
中科院分区:
化学1区
文献类型:
--
作者:
Lupoli, Tania J.;Tsukamoto, Hirokazu;Doud, Emma H.;Wang, Tsung-Shing Andrew;Walker, Suzanne;Kahne, Daniel

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β -内酰胺类抗生素是临床上最重要的一类抗生素。它们的致命靶点是青霉素结合蛋白(PBPs)的转肽酶结构域,它在细胞壁合成过程中催化细菌肽聚糖(PG)的交联。转肽化反应分两步进行,第一步是形成共价酶中间体,第二步是胺对中间体的攻击。在这里,我们使用定义的PG底物来解剖纯化的大肠杆菌转肽酶催化的单个步骤。我们证明这种转肽酶接受一组结构多样的d -氨基酸底物,并将它们整合到PG片段中。这些结果提供了供体和受体需求的新信息,以及先前观察到的非规范d -氨基酸可以引入细菌细胞壁的机制基础。
The beta-lactams are the most important class of antibiotics in clinical use. Their lethal targets are the transpeptidase domains of penicillin binding proteins (PBPs), which catalyze the crosslinking of bacterial peptidoglycan (PG) during cell wall synthesis. The transpeptidation reaction occurs in two steps, the first being formation of a covalent enzyme intermediate and the second involving attack of an amine on this intermediate. Here we use defined PG substrates to dissect the individual steps catalyzed by a purified E. coli transpeptidase. We demonstrate that this transpeptidase accepts a set of structurally diverse D-amino acid substrates and incorporates them into PG fragments. These results provide new information on donor and acceptor requirements as well as a mechanistic basis for previous observations that non-canonical D-amino acids can be introduced into the bacterial cell wall.
DOI: 10.1021/ja908916z
发表时间: 2009-12-30
影响因子: 15
作者:
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