title: Surface plasmon resonance--more than a screening technology: insights in the binding mode of σ70:core RNAP inhibitors.
abstract: OBJECTIVE
  Antibiotic resistance has become a major health problem. The σ(70):core interface of bacterial RNA polymerase is a promising drug target. Recently, the coiled-coil and lid-rudder-system of the β' subunit has been identified as an inhibition hot spot. Materials & methods & Results: By using surface plasmon resonance-based assays, inhibitors of the protein-protein interaction were identified and competition with σ(70) was shown. Effective inhibition was verified in an in vitro transcription and a σ(70):core assembly assay. For one hit series, we found a correlation between activity and affinity. Mutant interaction studies suggest the inhibitors' binding site.
  
  
  CONCLUSIONS
  Surface plasmon resonance is a valuable technology in drug design, that has been used in this study to identify and evaluate σ(70):core RNA polymerase inhibitors.
authors.affiliation: Department of Drug Design & Optimization, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus C2.3, D-66123 Saarbrücken, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Hüsecken
authors.forename: Stefan
authors.initials: S
authors.lastname: Hinsberger
authors.forename: Walid A M
authors.initials: WA
authors.lastname: Elgaher
authors.forename: Joerg
authors.initials: J
authors.lastname: Haupenthal
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D004926:Escherichia coli / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D011485:Protein Binding; D060066:Protein Interaction Maps / Q000187:drug effects; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology; D020349:Surface Plasmon Resonance; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D054852:Small Molecule Libraries; D012321:DNA-Directed RNA Polymerases