Repurposing p97 inhibitors for chemical modulation of the bacterial ClpB–DnaK bichaperone system
Przemysław Glaza, Chathurange B. Ranaweera, Sunitha Shiva, Anuradha Roy, Brian V. Geisbrecht, Frank J. Schoenen, Michal Žółkiewski
Abstract
∼5 μM and suppressed the growth of cultured Escherichia coli. The DBeQ-induced loss of E. coli proliferation was exacerbated by heat shock but was nearly eliminated in a ClpB-deficient E. coli strain, which demonstrates a significant selectivity of DBeQ toward ClpB in cells. Our results provide chemical validation of ClpB as a target for developing novel antimicrobials. We identified DBeQ as a promising lead compound for structural optimization aimed at selective targeting of ClpB and/or DnaK.
Topics & Concepts
CLPBBiologyAAA proteinsBacteriaATPaseBiochemistryMicrobiologyCell biologyEnzymeEscherichia coliGeneGeneticsHeat shock proteins researchBacterial Genetics and BiotechnologyATP Synthase and ATPases Research