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弹性蛋白酶LasB的小分子抑制剂的结构与结合模式

The Structures and Binding Modes of Small-Molecule Inhibitors of Elastase LasB.

作者信息

Camberlein Virgyl, Jézéquel Gwenaëlle, Haupenthal Jörg, Hirsch Anna K H

机构信息

Helmholtz Institute for Pharmaceutical Research Saarland (HIPS)-Helmholtz Centre for Infection Research (HZI), Campus E8.1, 66123 Saarbrücken, Germany.

Department of Pharmacy, Saarland University, Campus E8.1, 66123 Saarbrücken, Germany.

出版信息

Antibiotics (Basel). 2022 Aug 4;11(8):1060. doi: 10.3390/antibiotics11081060.

DOI:10.3390/antibiotics11081060
PMID:36009930
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9404851/
Abstract

Elastase B (LasB) is a zinc metalloprotease and a crucial virulence factor of . As the need for new strategies to fight antimicrobial resistance (AMR) constantly rises, this protein has become a key target in the development of novel antivirulence agents. The extensive knowledge of the structure of its active site, containing two subpockets and a zinc atom, led to various structure-based medicinal chemistry programs and the optimization of several chemical classes of inhibitors. This review provides a brief reminder of the structure of the active site and a summary of the disclosed LasB inhibitors. We specifically focused on the analysis of their binding modes with a detailed representation of them, hence giving an overview of the strategies aiming at targeting LasB by small molecules.

摘要

弹性蛋白酶B（LasB）是一种锌金属蛋白酶，也是……的关键毒力因子。随着对抗菌药物耐药性（AMR）新策略的需求不断增加，这种蛋白质已成为新型抗毒力药物开发的关键靶点。对其活性位点结构的广泛了解，该活性位点包含两个亚口袋和一个锌原子，催生了各种基于结构的药物化学项目以及对几类抑制剂的优化。本综述简要回顾了活性位点的结构，并总结了已公开的LasB抑制剂。我们特别着重于分析它们的结合模式并进行详细展示，从而概述了旨在通过小分子靶向LasB的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/529571fc3741/antibiotics-11-01060-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/b2902018dde7/antibiotics-11-01060-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/404ea533d2d9/antibiotics-11-01060-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/6349fbee3634/antibiotics-11-01060-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/336a858391c8/antibiotics-11-01060-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/f86d21992e9a/antibiotics-11-01060-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/a501d8b343f7/antibiotics-11-01060-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/2326b207482e/antibiotics-11-01060-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/7b95bb9607f9/antibiotics-11-01060-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/2221b889a3dc/antibiotics-11-01060-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/08d76d9fcaf6/antibiotics-11-01060-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/77099e9a15b4/antibiotics-11-01060-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/4b0ed674bdfe/antibiotics-11-01060-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/529571fc3741/antibiotics-11-01060-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/b2902018dde7/antibiotics-11-01060-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/404ea533d2d9/antibiotics-11-01060-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/6349fbee3634/antibiotics-11-01060-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/336a858391c8/antibiotics-11-01060-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/f86d21992e9a/antibiotics-11-01060-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/a501d8b343f7/antibiotics-11-01060-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/2326b207482e/antibiotics-11-01060-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/7b95bb9607f9/antibiotics-11-01060-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/2221b889a3dc/antibiotics-11-01060-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/08d76d9fcaf6/antibiotics-11-01060-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/77099e9a15b4/antibiotics-11-01060-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/4b0ed674bdfe/antibiotics-11-01060-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21db/9404851/529571fc3741/antibiotics-11-01060-g013.jpg

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