Antimicrobial lipopeptide tridecaptin A1 selectively binds to Gram-negative lipid II
Antimicrobial lipopeptide tridecaptin A1 selectively binds to Gram-negative lipid II
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DOI：
10.1073/pnas.1608623113
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发表时间：
2016-10-11
影响因子：
11.1
通讯作者：
Vederas, John C.
中科院分区：
文献类型：
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作者：
Cochrane, Stephen A.;Findlay, Brandon;Vederas, John C.
Tridecaptin A（1）（TriA（1））是一种非核糖体脂肽，对革兰氏阴性菌具有选择性抗菌活性。在这里，我们表明，TriA（1）发挥其杀菌作用，结合细菌细胞壁前体脂质II的内膜，破坏质子动力。生物化学和生物物理测定表明，结合到革兰氏阴性的脂质II的变体是膜破坏所需的，并且只有质子梯度被分散。已测定了TriA（1）在含有脂质II的十二烷基磷酸胆碱胶束中的NMR溶液结构，并使用分子模拟提供了TriA（1）-脂质II复合物的结构模型。这些结果表明，TriA（1）通过使用脂质-II结合基序的作用机制杀死革兰氏阴性菌。
Tridecaptin A(1) (TriA(1)) is a nonribosomal lipopeptide with selective antimicrobial activity against Gram-negative bacteria. Here we show that TriA(1) exerts its bactericidal effect by binding to the bacterial cell-wall precursor lipid II on the inner membrane, disrupting the proton motive force. Biochemical and biophysical assays show that binding to the Gram-negative variant of lipid II is required for membrane disruption and that only the proton gradient is dispersed. The NMR solution structure of TriA(1) in dodecylphosphocholine micelles with lipid II has been determined, and molecular modeling was used to provide a structural model of the TriA(1)-lipid II complex. These results suggest that TriA(1) kills Gram-negative bacteria by a mechanism of action using a lipid-II-binding motif.