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Crystal structure of MexZ, a key repressor responsible for antibiotic resistance in Pseudomonas aeruginosa

DOI: 10.1016/j.jsb.2010.07.012 DOI Help
PMID: 20691272 PMID Help

Authors: Y. Alguel (Imperial College MSF) , D. Lu (Imperial College London) , N. Quade (Imperial College London) , S. Sauter (Imperial College London) , X. Zhang (Imperial College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Structural Biology , VOL 172(3) , PAGES 305-310

State: Published (Approved)
Published: August 2010
Diamond Proposal Number(s): 1227

Abstract: Pseudomonas aeruginosa is responsible for around 10% of all hospital-acquired infections and the single most important pathogen of cystic fibrosis lungs. P. aeruginosa has high intrinsic and acquired antibiotic resistance, due to the extrusion of antibiotics by multidrug efflux pumps. The gene regulator MexZ controls the expression of mexXY, the efflux pump responsible for resistance to many drugs that are used for treating CF patients. MexZ is shown to be the most frequently mutated gene in P. aeruginosa isolated from CF patient lungs, confirming its importance in multidrug resistance. Here we present the crystal structure of MexZ at 2.9 Å. Combining the structural information with biochemical data on key mutants identified, we provide an explanation for the structural and functional consequences of these mutants. This work provides a framework for further characterisation of MexZ in order to fully understand its regulation and induction.

Journal Keywords: Crystallography; X-Ray; Cystic; DNA; Drug; Bacterial; Gene; Bacterial; Humans; Lung; Mutation; Protein; Secondary; Pseudomonas aeruginosa

Subject Areas: Biology and Bio-materials, Medicine, Chemistry


Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography , I04-Macromolecular Crystallography

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