Differential modes of peptide binding onto replicative sliding clamps from various bacterial origins

Philippe Wolff, Ismail Amal, Vincent Oliéric, Olivier Chaloin, Gudrun Gygli, Eric Ennifar, Bernard Lorber, Gilles Guichard, Jérôme Wagner, Annick Dejaegere, Dominique Y. Burnouf*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

31 Citations (Scopus)

Abstract

Bacterial sliding clamps are molecular hubs that interact with many proteins involved in DNA metabolism through their binding, via a conserved peptidic sequence, into a universally conserved pocket. This interacting pocket is acknowledged as a potential molecular target for the development of new antibiotics. We previously designed short peptides with an improved affinity for the Escherichia coli binding pocket. Here we show that these peptides differentially interact with other bacterial clamps, despite the fact that all pockets are structurally similar. Thermodynamic and modeling analyses of the interactions differentiate between two categories of clamps: group I clamps interact efficiently with our designed peptides and assemble the Escherichia coli and related orthologs clamps, whereas group II clamps poorly interact with the same peptides and include Bacillus subtilis and other Gram-positive clamps. These studies also suggest that the peptide binding process could occur via different mechanisms, which depend on the type of clamp.

Original languageEnglish
Pages (from-to)7565-7576
Number of pages12
JournalJournal of Medicinal Chemistry
Volume57
Issue number18
DOIs
Publication statusPublished - 25 Sept 2014

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