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http://purl.uniprot.org/citations/18812515http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18812515http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18812515http://www.w3.org/2000/01/rdf-schema#comment"The intrinsic antimicrobial resistance of the opportunistic human pathogen Pseudomonas aeruginosa is compounded in mutant strains that overexpress multidrug efflux pumps such as the prominent drug-proton antiporter, MexAB-OprM. The primary regulator of the mexAB-oprM operon is the MarR family repressor, MexR. An additional repressor, NalC, also regulates mexAB-oprM by controlling expression of ArmR, an antirepressor peptide that is hypothesized to prevent the binding of MexR to its cognate DNA operator via an allosteric protein-peptide interaction. To better understand how ArmR modulates MexR, we determined the MexR-binding region of ArmR as its C-terminal 25 residues and solved the crystal structure of MexR in a 2:1 complex with this ArmR fragment at 1.8 A resolution. This structure reveals that the C-terminal residues of ArmR form a kinked alpha-helix, which occupies a pseudosymmetrical and largely hydrophobic binding cavity located at the centre of the MexR dimer. Although the ArmR-binding cavity partially overlaps with the small molecule effector-binding sites of other MarR family members, it possesses a larger and more complex binding surface to accommodate the greater size and specific physicochemical properties of a peptide effector. Comparison with the structure of apo-MexR reveals that ArmR stabilizes a dramatic conformational change that is incompatible with DNA-binding. Thus, this work defines the structural mechanism by which ArmR allosterically derepresses MexR-controlled gene expression in P. aeruginosa and reveals important insights into the regulation of multidrug resistance."xsd:string
http://purl.uniprot.org/citations/18812515http://purl.org/dc/terms/identifier"doi:10.1073/pnas.0805489105"xsd:string
http://purl.uniprot.org/citations/18812515http://purl.org/dc/terms/identifier"doi:10.1073/pnas.0805489105"xsd:string
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/author"Strynadka N.C."xsd:string
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/author"Strynadka N.C."xsd:string
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/author"McIntosh L.P."xsd:string
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/author"McIntosh L.P."xsd:string
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/author"Creagh A.L."xsd:string
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/author"Creagh A.L."xsd:string
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/author"Haynes C.A."xsd:string
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/author"Haynes C.A."xsd:string
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/author"Wilke M.S."xsd:string
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/author"Wilke M.S."xsd:string
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/author"Poole K."xsd:string
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/author"Poole K."xsd:string
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/author"Heller M."xsd:string
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/author"Heller M."xsd:string
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/name"Proc. Natl. Acad. Sci. U.S.A."xsd:string
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/name"Proc Natl Acad Sci U S A"xsd:string
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/pages"14832-14837"xsd:string
http://purl.uniprot.org/citations/18812515http://purl.uniprot.org/core/pages"14832-14837"xsd:string