title: A target-protection mechanism of antibiotic resistance at atomic resolution: insights into FusB-type fusidic acid resistance.
abstract: Antibiotic resistance in clinically important bacteria can be mediated by proteins that physically associate with the drug target and act to protect it from the inhibitory effects of an antibiotic. We present here the first detailed structural characterization of such a target protection mechanism mediated through a protein-protein interaction, revealing the architecture of the complex formed between the FusB fusidic acid resistance protein and the drug target (EF-G) it acts to protect. Binding of FusB to EF-G induces conformational and dynamic changes in the latter, shedding light on the molecular mechanism of fusidic acid resistance.
authors.affiliation: School of Molecular and Cellular Biology, Garstang Building, University of Leeds, Leeds, UK, LS2 9JT.|Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK, LS2 9JT.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Tomlinson
authors.affiliation: School of Molecular and Cellular Biology, Garstang Building, University of Leeds, Leeds, UK, LS2 9JT.|Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK, LS2 9JT.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Thompson
authors.affiliation: School of Molecular and Cellular Biology, Garstang Building, University of Leeds, Leeds, UK, LS2 9JT.|Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK, LS2 9JT.
authors.forename: Arnout P
authors.initials: AP
authors.lastname: Kalverda
authors.affiliation: School of Molecular and Cellular Biology, Garstang Building, University of Leeds, Leeds, UK, LS2 9JT.|Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK, LS2 9JT.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Zhuravleva
authors.affiliation: School of Molecular and Cellular Biology, Garstang Building, University of Leeds, Leeds, UK, LS2 9JT.|Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK, LS2 9JT.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: O'Neill
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D016503:Drug Delivery Systems / Q000379:methods; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005672:Fusidic Acid / Q000494:pharmacology*; D020653:Peptide Elongation Factor G / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D054730:Protein Interaction Domains and Motifs / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D020653:Peptide Elongation Factor G; D005672:Fusidic Acid