Discovery of novel SecA inhibitors of Candidatus Liberibacter asiaticus by structure based design

被引：37

作者：

Akula, Nagaraju ^{[1
]}

Zheng, Hong ^{[2
]}

Han, Frank Q. ^{[2
]}

Wang, Nian ^{[1
]}

机构：

[1] Univ Florida, Citrus Res & Educ Ctr, Dept Microbiol & Cell Sci, Lake Alfred, FL 33850 USA

[2] Struct Based Design Inc, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 14期

关键词：

SecA; Virtual screening; Structure; Molecular docking; Inhibitors; CITRUS; COLI; PHOSPHOLIPIDS; BACTERIUM; PROTEINS; DOCKING; DISEASE; GLIDE;

D O I：

10.1016/j.bmcl.2011.05.086

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Candidatus Liberibacter asiaticus is the causal agent of Huanglongbing (HLB) disease of citrus. Current management practices have not been able to control HLB and stop the spread of HLB. The current study is focused on screening small molecule inhibitors against SecA protein of Ca. L. asiaticus. Homology modeling, structure based virtual screening and molecular docking methods have been used to find the novel inhibitory compounds against SecA activity at ATP binding region. At 20 mu m 17 compounds showed >50% inhibition and four compounds had more than 65% inhibition. The most active compound has IC(50) value of 2.5 mu M. The differences between the activities of the compounds are explained by their inter-molecular interactions at ATP binding site. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：4183 / 4188

页数：6

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