The Mechanism of Caseinolytic Protease (ClpP) Inhibition1. Issue 10 (30th January 2013)

• Record Type: Journal Article
• Authors: Gersch, Malte; Gut, Felix; Korotkov, Vadim S.; Lehmann, Johannes; Böttcher, Thomas; Rusch, Marion; Hedberg, Christian; Waldmann, Herbert; Klebe, Gerhard; Sieber, Stephan A.
• Is Part Of: Angewandte Chemie international edition. Volume 52:Issue 10(2013)
• Page Start: 3009
• Page End: 3014
• Publication Date: 2013-01-30
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201204690
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="graphical" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold>Catch me if you can</bold>: The ClpP protease mediates protein homeostasis and can be efficiently inhibited by β‐lactones. A combination of molecular docking, mutagenesis, activity‐based protein profiling, and kinetics studies now reveals the mechanism of ClpP inhibition. A hydrophobic pocket next to the active site allows binding of long aliphatic and aromatic residues. The preferred stereoisomer binds into the oxyanion hole.<boxed-text content-type="graphic" position="anchor" orientation="portrait"><graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgg1ts9s8br" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></boxed-text></p> </abstract>