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Crystal structure of the transcriptional regulator AcrR from Escherichia coli.

Li M, Gu R, Su CC, Routh MD, Harris KC, Jewell ES, McDermott G, Yu EW
J Mol Biol 374 591-603 (2007)
Cited: 52 times
EuropePMC logo PMID: 17950313

Abstract

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-A 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 A(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.

Reviews - 2qop mentioned but not cited (1)

  1. The TetR family of regulators. Cuthbertson L, Nodwell JR. Microbiol Mol Biol Rev 77 440-475 (2013)

Articles - 2qop mentioned but not cited (2)

  1. Conformational change of the AcrR regulator reveals a possible mechanism of induction. Gu R, Li M, Su CC, Long F, Routh MD, Yang F, McDermott G, Yu EW. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 64 584-588 (2008)
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  18. Unraveling the specific regulation of the central pathway for anaerobic degradation of 3-methylbenzoate. Juárez JF, Liu H, Zamarro MT, McMahon S, Liu H, Naismith JH, Eberlein C, Boll M, Carmona M, Díaz E. J. Biol. Chem. 290 12165-12183 (2015)
  19. A scalable metabolite supplementation strategy against antibiotic resistant pathogen Chromobacterium violaceum induced by NAD+/NADH+ imbalance. Banerjee D, Parmar D, Bhattacharya N, Ghanate AD, Panchagnula V, Raghunathan A. BMC Syst Biol 11 51 (2017)
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  36. The Multidrug Efflux Regulator AcrR of Escherichia coli Responds to Exogenous and Endogenous Ligands To Regulate Efflux and Detoxification. Harmon DE, Ruiz C. mSphere 7 e0047422 (2022)
  37. The crystal structure of AcrR from Mycobacterium tuberculosis reveals a one-component transcriptional regulation mechanism. Kang SM, Kim DH, Jin C, Ahn HC, Lee BJ. FEBS Open Bio 9 1713-1725 (2019)
  38. The multidrug efflux pump regulator AcrR directly represses motility in Escherichia coli. Maldonado J, Czarnecka B, Harmon DE, Ruiz C. mSphere 8 e0043023 (2023)
  39. The two-Cys-type TetR repressor GbaA confers resistance under disulfide and electrophile stress in Staphylococcus aureus. Van Loi V, Busche T, Fritsch VN, Weise C, Gruhlke MCH, Slusarenko AJ, Kalinowski J, Antelmann H. Free Radic Biol Med 177 120-131 (2021)


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