Structure based discovery of small molecule suppressors targeting bacterial lysozyme inhibitors

被引:17
作者
Voet, Arnout [1 ]
Callewaert, Lien [2 ,3 ]
Ulens, Tim [1 ]
Vanderkelen, Lise [2 ,3 ]
Vanherreweghe, Joris M. [2 ,3 ]
Michiels, Chris W. [2 ,3 ]
De Maeyer, Marc [1 ]
机构
[1] Katholieke Univ Leuven, Lab Biomol Modelling & BioMacS, B-3001 Louvain, Belgium
[2] Katholieke Univ Leuven, Food Microbiol Lab, B-3001 Louvain, Belgium
[3] Katholieke Univ Leuven, Leuven Food Sci & Nutr Res Ctr LFoRCe, B-3001 Louvain, Belgium
关键词
Salmonella; PliC; MliC; Pharmacophore; Docking; Drug design; SMPPII; PROTEIN-PROTEIN INTERACTIONS; GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; EGG-WHITE; PEPTIDOGLYCAN; IVY; RECOGNITION; SPECIFICITY; RESISTANCE;
D O I
10.1016/j.bbrc.2011.01.053
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The production of lysozyme inhibitors, competitively binding to the lysozyme active site, is a bacterial strategy to prevent the lytic activity of host lysozymes. Therefore, suppression of the lysozyme-inhibitor interaction is an interesting new approach for drug development since restoration of the bacterial lysozyme sensitivity will support bacterial clearance from the infected sites. Using molecular modelling techniques the interaction of the Salmonella PliC inhibitor with c-type lysozyme was studied and a protein-protein interaction based pharmacophore model was created. This model was used as a query to identify molecules, with potential affinity for the target, and subsequently, these molecules were filtered using molecular docking. The retained molecules were validated as suppressors of lysozyme inhibitory proteins using in vitro experiments revealing four active molecules. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:527 / 532
页数:6
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