Selectivity profiling of DegP substrates and inhibitors

被引：34

作者：

Hauske, Patrick ^{[1
,2
]}

Meltzer, Michael ^{[2
]}

Ottmann, Christian ^{[1
]}

Krijer, Tobias ^{[3
]}

Clausen, Tim ^{[3
]}

Ehrmann, Michael ^{[2
,4
]}

Kaiser, Markus ^{[1
]}

机构：

[1] Max Planck Gesell, Chem Genom Ctr, D-44227 Dortmund, Germany

[2] Univ Duisburg Essen, FB Biol & Geog, Zentrum Med Biotechnol, D-45117 Essen, Germany

[3] Res Inst Mol Pathol IMP, A-1030 Vienna, Austria

[4] Cardiff Univ, Cardiff Sch Biosci, Cardiff CF10 3US, S Glam, Wales

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 07期

基金：

英国生物技术与生命科学研究理事会;

关键词：

HtrA protease; DegP; Allosteric regulation; Substrate; Inhibitor; STRUCTURAL BASIS; PROTEASE; CHAPERONE; SPECIFICITY;

D O I：

10.1016/j.bmc.2009.01.073

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Protein quality control factors are involved in many key physiological processes and severe human diseases that are based on misfolding or amyloid formation. Prokaryotic representatives are often virulence factors of pathogenic bacteria. Therefore, protein quality control factors represent a novel class of drug targets. The bacterial serine protease DegP, belonging to the widely conserved family of HtrA proteases, exhibits unusual structural and functional plasticity that could be exploited by small molecule modulators. However, only one weak synthetic peptide substrate and no inhibitors are available to date. We report the identification of a potent heptameric pNA-substrate and chloromethyl ketone based inhibitors of DegP. In addition, specificity profiling resulted in the identification of one strong inhibitor and a potent substrate for subtilisin as well as a number of specific elastase substrates and inhibitors. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：2920 / 2924

页数：5

共 16 条

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