Novel inhibitor discovery and the conformational analysis of inhibitors of listeriolysin O via protein-ligand modeling.
Novel inhibitor discovery and the conformational analysis of inhibitors of listeriolysin O via protein-ligand modeling.
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DOI：
10.1038/srep08864
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发表时间：
2015-03-09
影响因子：
4.6
通讯作者：
Niu X
中科院分区：
文献类型：
--
作者：
Wang J;Zhou X;Liu S;Li G;Zhang B;Deng X;Niu X
细菌对可用抗生素的耐药性增加使得发现新的有效抗菌剂成为优先事项。以往的研究表明，溶血素O（LLO）是一个关键的毒力因子，并建议它是一个目标，开发抗单增李斯特菌感染的毒力药物。本文报道了利用溶血试验发现具有差异活性的LLO天然化合物抑制剂。抑制剂的作用机制与非瑟酮一致，非瑟酮是一种没有抗菌活性的天然黄酮类化合物，我们在以前的报告中通过分子模拟显示了这一点。此外，当抑制剂分子中的单键（C1-C2）被双键（C1-C2）取代时，观察到抗溶血活性的显著增加。这种变化是基于配体-残基相互作用的分解，这表明抑制剂中的双键（C1-C2）是其抑制LLO所必需的。目前的MD模拟工作提供了深入了解的机制，通过该化合物抑制LLO在原子水平上，将是有用的新的，选择性LLO抑制剂的开发。
Increasing bacterial resistance to available antibiotics makes the discovery of novel efficacious antibacterial agents a priority. A previous report showed that listeriolysin O (LLO) is a critical virulence factor and suggested that it is a target for developing anti-virulence drugs against Listeria monocytogenes infections. In this study, we report the discovery of LLO natural compound inhibitors with differential activity by using hemolysis assay. The mechanism of action of the inhibitors was consistent with that of fisetin, a natural flavonoid without antimicrobial activity, which we showed in our previous report via molecular simulation. Furthermore, a substantial increase in anti-hemolytic activity was observed when the single bond (C1-C2) was replaced by a double bond (C1-C2) in the inhibitor molecule. This change was based on the decomposition of the ligand-residue interaction, which indicated that the double bond (C1-C2) in the inhibitors was required for their inhibition of LLO. The current MD simulation work provides insights into the mechanism by which the compounds inhibit LLO at the atomic level and will be useful for the development of new, selective LLO inhibitors.
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血素素在单核细胞增生李斯特菌的细胞内生长中的作用。
DOI：
10.1084/jem.167.4.1459
发表时间：
1988-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Portnoy DA;Jacks PS;Hinrichs DJ
通讯作者：
Hinrichs DJ
影响因子：
6.4
作者：
Qiu, Jiazhang;Niu, Xiaodi;Deng, Xuming
通讯作者：
Deng, Xuming
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML
影响因子：
3.1
作者：
GAILLARD, JL;BERCHE, P;SANSONETTI, P
通讯作者：
SANSONETTI, P
影响因子：
3
作者：
Morris, Garrett M.;Huey, Ruth;Lindstrom, William;Sanner, Michel F.;Belew, Richard K.;Goodsell, David S.;Olson, Arthur J.
通讯作者：
Olson, Arthur J.