Crystal structure of the transcriptional regulator AcrR from Escherichia coli

[摘要] The AcrAB multidrug efflux pump, which belongs to the resistance nodulation division (RND) family, recognizes and extrudes a wide range of antibiotics and chemotherapeutic agents and causes the intrinsic antibiotic resistance in Escherichia coli. The expression of AcrAB is controlled by the transcriptional regulator AcrR, whose open reading frame is located 141 bp upstream of the acrAB operon. To understand the structural basis of AcrR regulation, we have determined the crystal structure of AcrR to 2.55-angstrom resolution, revealing a dimeric two-domain molecule with an entirely helical architecture similar to members of the TetR family of transcriptional regulators. Each monomer of AcrR forms a multientrance pocket of 350 angstrom(3) in the ligand-binding domain. The ligand-binding pocket is surrounded with mostly hydrophobic residues. In addition,, a completely buried negatively charged glutamate, expected to be critical for drug binding, is located at the center of the binding pocket. The crystal structure provides novel insight into the mechanisms of ligand binding and AcrR regulation. (c) 2007 Elsevier Ltd. All rights reserved.

[发布日期] 2007-11-30

[关键词] TetR family;Escherichia coli AcrR;transcriptional regulator;X-ray crystallograhy;multidrug resistance