title: Differential modes of peptide binding onto replicative sliding clamps from various bacterial origins.
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.
authors.affiliation: Université de Strasbourg , UPR9002, Architecture et Réactivité de l'ARN, Institut de Biologie Moléculaire et Cellulaire du CNRS, 15, rue René Descartes, 67084 Strasbourg, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Wolff
authors.forename: Ismail
authors.initials: I
authors.lastname: Amal
authors.forename: Vincent
authors.initials: V
authors.lastname: Oliéric
authors.forename: Olivier
authors.initials: O
authors.lastname: Chaloin
authors.forename: Gudrun
authors.initials: G
authors.lastname: Gygli
authors.forename: Eric
authors.initials: E
authors.lastname: Ennifar
authors.forename: Bernard
authors.initials: B
authors.lastname: Lorber
authors.forename: Gilles
authors.initials: G
authors.lastname: Guichard
authors.forename: Jérôme
authors.initials: J
authors.lastname: Wagner
authors.forename: Annick
authors.initials: A
authors.lastname: Dejaegere
authors.forename: Dominique Y
authors.initials: DY
authors.lastname: Burnouf
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism; D001419:Bacteria / Q000235:genetics* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004261:DNA Replication; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D016415:Sequence Alignment; D013816:Thermodynamics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010455:Peptides