title: Identification of inhibitors of bacterial RNA polymerase.
abstract: Very few clinically available antibiotics target bacterial RNA polymerase (RNAP) suggesting it is an underutilized target. The advent of detailed structural information of RNAP holoenzyme (HE) has allowed the design and in silico screening of novel transcription inhibitors. Here, we describe our approach for the design and testing of small molecule transcription inhibitors that work by preventing the interaction between the essential transcription initiation factor σ and RNAP. With the appropriate structural information this approach can be easily modified to other essential protein-protein interactions.
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Cong
authors.initials: C
authors.lastname: Ma
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia. Electronic address: Peter.Lewis@newcastle.edu.au.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lewis
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics*; D020035:Holoenzymes / Q000737:chemistry / Q000187:drug effects; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry / Q000648:ultrastructure; D011401:Promoter Regions, Genetic; D060066:Protein Interaction Maps / Q000187:drug effects; D012808:Sigma Factor / Q000737:chemistry / Q000235:genetics*; D054852:Small Molecule Libraries / Q000737:chemistry*; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D020035:Holoenzymes; D046911:Macromolecular Substances; D012808:Sigma Factor; D054852:Small Molecule Libraries; D012321:DNA-Directed RNA Polymerases
keywords: Protein–protein interaction; RNA polymerase; Small molecule inhibitors; Transcription initiation