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The Mechanism of Caseinolytic Protease (ClpP) Inhibition
Author(s) -
Gersch Malte,
Gut Felix,
Korotkov Vadim S.,
Lehmann Johannes,
Böttcher Thomas,
Rusch Marion,
Hedberg Christian,
Waldmann Herbert,
Klebe Gerhard,
Sieber Stephan A.
Publication year - 2013
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201204690
Subject(s) - protease , chemistry , computational biology , mechanism (biology) , mutagenesis , docking (animal) , biochemistry , computer science , world wide web , biology , mutant , enzyme , gene , medicine , nursing , philosophy , epistemology
Catch me if you can : 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.