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Structural contributions to multidrug recognition in the multidrug resistance (MDR) gene regulator, BmrR.

Bachas S, Eginton C, Gunio D, Wade H
Proc Natl Acad Sci U S A 108 11046-51 (2011)
Related entries: 3q1m, 3q3d, 3q5p, 3q5r, 3q5s

Cited: 23 times
EuropePMC logo PMID: 21690368

Abstract

Current views of multidrug (MD) recognition focus on large drug-binding cavities with flexible elements. However, MD recognition in BmrR is supported by a small, rigid drug-binding pocket. Here, a detailed description of MD binding by the noncanonical BmrR protein is offered through the combined use of X-ray and solution studies. Low shape complementarity, suboptimal packing, and efficient burial of a diverse set of ligands is facilitated by an aromatic docking platform formed by a set of conformationally fixed aromatic residues, hydrophobic pincer pair that locks the different drug structures on the adaptable platform surface, and a trio of acidic residues that enables cation selectivity without much regard to ligand structure. Within the binding pocket is a set of BmrR-derived H-bonding donor and acceptors that solvate a wide range of ligand polar substituent arrangements in a manner analogous to aqueous solvent. Energetic analyses of MD binding by BmrR are consistent with structural data. A common binding orientation for the different BmrR ligands is in line with promiscuous allosteric regulation.

Reviews - 3q2y mentioned but not cited (1)

  1. Bacterial MerR family transcription regulators: activationby distortion. Fang C, Zhang Y. Acta Biochim Biophys Sin (Shanghai) 54 25-36 (2022)

Articles - 3q2y mentioned but not cited (1)

  1. Structural contributions to multidrug recognition in the multidrug resistance (MDR) gene regulator, BmrR. Bachas S, Eginton C, Gunio D, Wade H. Proc. Natl. Acad. Sci. U.S.A. 108 11046-11051 (2011)


Reviews citing this publication (2)

  1. Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria. Sionov RV, Steinberg D. Microorganisms 10 1239 (2022)
  2. Emerging role of nuclear factor erythroid 2-related factor 2 in the mechanism of action and resistance to anticancer therapies. Paramasivan P, Kankia IH, Langdon SP, Deeni YY. Cancer Drug Resist 2 490-515 (2019)

Articles citing this publication (19)

  1. Structures of a Na+-coupled, substrate-bound MATE multidrug transporter. Lu M, Symersky J, Radchenko M, Koide A, Guo Y, Nie R, Koide S. Proc. Natl. Acad. Sci. U.S.A. 110 2099-2104 (2013)
  2. Transported substrate determines exchange rate in the multidrug resistance transporter EmrE. Morrison EA, Henzler-Wildman KA. J. Biol. Chem. 289 6825-6836 (2014)
  3. Plant Lessons: Exploring ABCB Functionality Through Structural Modeling. Bailly A, Yang H, Martinoia E, Geisler M, Murphy AS. Front Plant Sci 2 108 (2011)
  4. The bacterial multidrug resistance regulator BmrR distorts promoter DNA to activate transcription. Fang C, Li L, Zhao Y, Wu X, Philips SJ, You L, Zhong M, Shi X, O'Halloran TV, Li Q, Zhang Y. Nat Commun 11 6284 (2020)
  5. Antibiotic binding of STY3178, a yfdX protein from Salmonella Typhi. Saha P, Manna C, Das S, Ghosh M. Sci Rep 6 21305 (2016)
  6. Structural Analysis of the Hg(II)-Regulatory Protein Tn501 MerR from Pseudomonas aeruginosa. Wang D, Huang S, Liu P, Liu X, He Y, Chen W, Hu Q, Wei T, Gan J, Ma J, Chen H. Sci Rep 6 33391 (2016)
  7. Structural basis of copper-efflux-regulator-dependent transcription activation. Shi W, Zhang B, Jiang Y, Liu C, Zhou W, Chen M, Yang Y, Hu Y, Liu B. iScience 24 102449 (2021)
  8. BrlR from Pseudomonas aeruginosa is a receptor for both cyclic di-GMP and pyocyanin. Wang F, He Q, Yin J, Xu S, Hu W, Gu L. Nat Commun 9 2563 (2018)
  9. Charge is Major Determinant of Activation of the Ligand-Responsive Multidrug Resistance Gene Regulator, BmrR. Bachas S, Kohrs B, Wade H. ChemMedChem 11 1038-1041 (2016)
  10. Crystal structure of BrlR with c-di-GMP. Raju H, Sharma R. Biochem. Biophys. Res. Commun. 490 260-264 (2017)
  11. Identification of Position-Specific Correlations between DNA-Binding Domains and Their Binding Sites. Application to the MerR Family of Transcription Factors. Korostelev YD, Zharov IA, Mironov AA, Rakhmaininova AB, Gelfand MS. PLoS ONE 11 e0162681 (2016)
  12. Unconventional Coupling between Ligand Recognition and Allosteric Control in the Multidrug Resistance Gene Regulator, BmrR. Bachas S, Kohrs B, Wade H. ChemMedChem 12 426-430 (2017)
  13. A Specialized Polythioamide-Binding Protein Confers Antibiotic Self-Resistance in Anaerobic Bacteria. Gude F, Molloy EM, Horch T, Dell M, Dunbar KL, Krabbe J, Groll M, Hertweck C. Angew Chem Int Ed Engl 61 e202206168 (2022)
  14. GyrI-like proteins catalyze cyclopropanoid hydrolysis to confer cellular protection. Yuan H, Zhang J, Cai Y, Wu S, Yang K, Chan HCS, Huang W, Jin WB, Li Y, Yin Y, Igarashi Y, Yuan S, Zhou J, Tang GL. Nat Commun 8 1485 (2017)
  15. Reversal of doxorubicin resistance in lung cancer cells by neferine is explained by nuclear factor erythroid-derived 2-like 2 mediated lung resistance protein down regulation. Paramasivan P, Kumar JD, Baskaran R, Weng CF, Padma VV. Cancer Drug Resist 3 647-665 (2020)
  16. Antibiotic binding releases autoinhibition of the TipA multidrug-resistance transcriptional regulator. Jiang X, Zhang L, Teng M, Li X. J Biol Chem 295 17865-17876 (2020)
  17. Chemotaxis of the Human Pathogen Pseudomonas aeruginosa to the Neurotransmitter Acetylcholine. Matilla MA, Velando F, Tajuelo A, Martín-Mora D, Xu W, Sourjik V, Gavira JA, Krell T. mBio 13 e0345821 (2022)
  18. Classification of ligand molecules in PDB with graph match-based structural superposition. Shionyu-Mitsuyama C, Hijikata A, Tsuji T, Shirai T. J. Struct. Funct. Genomics 17 135-146 (2016)
  19. Molecular insights into antibiotic resistance - how a binding protein traps albicidin. Rostock L, Driller R, Grätz S, Kerwat D, von Eckardstein L, Petras D, Kunert M, Alings C, Schmitt FJ, Friedrich T, Wahl MC, Loll B, Mainz A, Süssmuth RD. Nat Commun 9 3095 (2018)


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