The Mechanism of Caseinolytic Protease (ClpP) Inhibition
Angewandte Chemie, 2013, DOI: 10.1002/ange.201204690, Volume 125, Issue 10, pages 3083–3088 published on 04.03.2013
Maintaining homeostasis at the protein level is an important prerequisite for cellular viability for which prokaryotes exhibit several proteolytic machineries, including ClpXP. In 2008, we reported the first small-molecule inhibitor for the proteolytic subunit ClpP and demonstrated that the inhibition of the enzyme in living bacteria significantly attenuates their capability to produce virulence factors, such as life-threatening toxins. Although ClpP has been extensively studied by biochemical and structural methods, the mechanism of small-molecule inhibition of this enzyme is currently poorly understood.