3ech

The MarR-family repressor MexR in complex with its antirepressor ArmR

spinqualitylabelsall models 3ech, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ech is a 3 chain structure with sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.802Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MEXR_PSEAE Repressor of the mexAB-oprM multidrug resistance operon. Also represses its own expression. Many variants lead to increased expression of the mexAB-oprM operon. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. The crystal structure of MexR from Pseudomonas aeruginosa in complex with its antirepressor ArmR.,Wilke MS, Heller M, Creagh AL, Haynes CA, McIntosh LP, Poole K, Strynadka NC Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):14832-7. Epub 2008 Sep 23. PMID:18812515 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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