Publication Abstract from PubMed
The molecular chaperone DnaK assists protein folding and refolding, translocation across membranes, and regulation of the heat shock response. In Escherichia coli, the protein is a target for insect-derived antimicrobial peptides, pyrrhocoricins. We present here the X-ray crystallographic analysis of the E. coli DnaK substrate-binding domain in complex with pyrrhocoricin-derived peptide inhibitors. The structures show that pyrrhocoricins act as site-specific, dual-mode (competitive and allosteric) inhibitors, occupying the substrate-binding tunnel and disrupting the latch between the lid and the beta-sandwich. Our structural analysis revealed an allosteric coupling between the movements of the lid and the interdomain linker, identifying a previously unknown mechanism of the lid-mediated regulation of the chaperone cycle.
Allosteric coupling between the lid and interdomain linker in DnaK revealed by inhibitor binding studies.,Liebscher M, Roujeinikova A J Bacteriol. 2009 Mar;191(5):1456-62. Epub 2008 Dec 19. PMID:19103929[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
