QacR-cation recognition is mediated by a redundancy of residues capable of charge neutralization

Biochemistry

Volumn 47, Issue 31, 2008, Pages 8122-8129

  Peters, Kate M ^a   Schuman, Jason T ^b   Skurray, Ronald A ^a   Brown, Melissa H ^a,c   Brennan, Richard G ^b   Schumacher, Maria A ^b  

^a UNIVERSITY OF SYDNEY   (Australia)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^c FLINDERS UNIVERSITY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACIDS; AROMATIC COMPOUNDS; BINDING ENERGY; CHEMOTHERAPY; DRUG DELIVERY; DRUG DOSAGE; NONMETALS; OXYGEN; POLYPEPTIDES; QUALITY ASSURANCE; REDUNDANCY; RELIABILITY;

AROMATIC RESIDUES; BINDING POCKETS; BINDING PROTEINS; BIOCHEMICAL EFFECTS; BROAD SPECTRUM; CATIONIC DRUGS; CHARGE NEUTRALIZATION; DRUG BINDING; GLUTAMIC ACID RESIDUES; LIPOPHILIC DRUGS; OXYGEN ATOMS; POSITIVE CHARGES; POSITIVELY CHARGED; SIDE CHAINS; STAPHYLOCOCCUS AUREUS;

DRUG INTERACTIONS;

ALANINE; BERBERINE; CATION; DEQUALINIUM; DIVALENT CATION; GLUTAMIC ACID; GLUTAMINE; OXYGEN; QACR PROTEIN;

AMINO ACID SUBSTITUTION; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG PROTEIN BINDING; ELECTRICITY; MOLECULAR RECOGNITION; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN STRUCTURE; REDUNDANCY ANALYSIS; STRUCTURE ANALYSIS;

BACTERIAL PROTEINS; BERBERINE; BINDING SITES; CALORIMETRY; CATIONS; CRYSTALLOGRAPHY, X-RAY; MUTATION; POLYMERASE CHAIN REACTION; PROTEIN BINDING; PROTEIN STRUCTURE, SECONDARY; REPRESSOR PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

STAPHYLOCOCCUS AUREUS;

EID: 48649104875     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi8008246     Document Type: Article

References (36)

1. Ramos, J. L., Martinez-Bueno, M., Molina-Henares, A. J., Teran, W., Watanabe, K., Zhang, X., Gallegos, M. T., Brennan, R., and Tobes, R. (2005) The TetR family of transcriptional repressors. Microbiol. Mol. Biol. Rev. 69, 326-356.
2. Grkovic, S., Brown, M. H., and Skurray, R. A. (2002) Regulation of bacterial drug export systems. Microbiol. Mol. Biol. Rev. 66, 671-701.
3. Rouch, D. A., Cram, D. S., DiBerardino, D., Littlejohn, T. G., and Skurray, R. A. (1990) Efflux-mediated antiseptic resistance gene qacA from Staphylococcus aureus: Common ancestry with tetracycline- and sugar-transport proteins. Mol. Microbiol. 4, 2051-2062.
4. Grkovic, S., Brown, M. H., Schumacher, M. A., Brennan, R. G., and Skurray, R. A. (2001) The staphylococcal QacR multidrug regulator binds a correctly spaced operator as a pair of dimers. J. Bacteriol. 183, 7102-7109.
5. Schumacher, M. A., Miller, M. C., Grkovic, S., Brown, M. H., Skurray, R. A., and Brennan, R. G. (2002) Structural basis for cooperative DNA binding by two dimers of the multidrug binding protein QacR. EMBO J. 21, 1210-1218.
6. Grkovic, S., Brown, M. H., Roberts, N. J., Paulsen, I. T., and Skurray, R. A. (1998) QacR is a repressor protein that regulates expression of the Staphylococcus aureus multidrug efflux pump QacA. J. Biol. Chem. 273, 18665-18673.
7. Grkovic, S., Hardie, K. M., Brown, M. H., and Skurray, R. A. (2003) Interactions of the QacR multidrug-binding protein with structurally diverse ligands: Implications for the evolution of the binding pocket. Biochemistry 42, 15226-15236.
8. Schumacher, M. A., Miller, M. C., Grkovic, S., Brown, M. H., Skurray, R. A., and Brennan, R. G. (2001) Structural mechanisms of QacR induction and multidrug recognition. Science 294, 2158-2163.
9. Yu, E. W., McDermott, G., Zgurskaya, H. I., Nikaido, H., and Koshland, D. E., Jr. (2003) Structural basis of multiple drug-binding capacity of the AcrB multidrug efflux pump. Science 300, 976-980.
10. Murakami, S., Nakashima, R., Yamashita, E., Matsumoto, T., and Yamaguchi, A. (2006) Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature 443, 173-179.
11. Vázquez-Laslop, N., Markham, P. N., and Neyfakh, A. A. (1999) Mechanism of ligand recognition by BmrR, the multidrug-responding transcriptional regulator: Mutational analysis of the ligand-binding site. Biochemistry 38, 16925-16931.
12. Edgar, R., and Bibi, E. (1999) A single membrane-embedded negative charge is critical for recognizing positively charged drugs by the Escherichia coli multidrug resistance protein MdfA. EMBO J. 18, 822-832.
13. Muth, T. R., and Schuldiner, S. (2000) A membrane-embedded glutamate is required for ligand binding to the multidrug transporter EmrE. EMBO J. 19, 234-240.
14. Paulsen, I. T., Brown, M. H., Littlejohn, T. G., Mitchell, B. A., and Skurray, R. A. (1996) Multidrug resistance proteins QacA and QacB from Staphylococcus aureus: Membrane topology and identification of residues involved in substrate specificity. Proc. Natl. Acad. Sci. U.S.A. 93, 3630-3635.
15. Mitchell, B. A., Paulsen, I. T., Brown, M. H., and Skurray, R. A. (1999) Bioenergetics of the staphylococcal multidrug export protein QacA: Identification of distinct binding sites for monovalent and divalent cations. J. Biol. Chem. 274, 3541-3548.
16. Zhang, D. W., Cole, S. P., and Deeley, R. G. (2001) Identification of a nonconserved amino acid residue in multidrug resistance protein 1 important for determining substrate specificity: Evidence for functional interaction between transmembrane helices 14 and 17. J. Biol. Chem. 276, 34966-34974.
17. Sambrook, J., Fritsch, E. F., and Maniatis, T. (1989) Molecular Cloning: A Laboratory Manual, 2nd ed., Cold Spring Harbor Laboratory Press, Plainview, NY.
18. Brooks, B. E., Piro, K. M., and Brennan, R. G. (2007) Multidrug-binding transcription factor QacR binds the bivalent aromatic diamidines DB75 and DB359 in multiple positions. J. Am. Chem. Soc. 129, 8389-8395.
19. Rayment, I. (1997) Reductive alkylation of lysine residues to alter crystallization properties of proteins. Methods Enzymol. 276, 171-179.
20. Collaborative Computational Project, Number 4 (1994) The CCP4 suite: Programs for protein crystallography. Acta Crystallogr. D50, 760-763.
21. Leslie, A. G. W. (1992) Recent changes to the MOSFLM package for processing film and image plate data. Newsletter of Protein Crystallography 26.
22. Brunger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse-Kunstleve, R. W., Jiang, J. S., Kuszewski, J., Nilges, M., Pannu, N. S., Read, R. J., Rice, L. M., Simonson, T., and Warren, G. L. (1998) Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr. D54, 905-921.
23. Jones, T. A., Zou, J. Y., Cowan, S. W., and Kjeldgaard, M. (1991) Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr. 47 (Part 2), 110-119.
24. Laskowski, R. A., MacArthur, M. W., Moss, D. S., and Thornton, J. M. (1993) PROCHECK: A program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 26, 283-291.
25. Delano, W. L. (2006) The PyMOL Molecular Graphics System, DeLano Scientific, Palo Alto, CA.
26. Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., and Ferrin, T. E. (2004) UCSF Chimera: A visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605-1612.
27. Murray, D. S., Schumacher, M. A., and Brennan, R. G. (2004) Crystal structures of QacR-diamidine complexes reveal additional multidrug-binding modes and a novel mechanism of drug charge neutralization. J. Biol. Chem. 279, 14365-14371.
28. Schumacher, M. A., Miller, M. C., and Brennan, R. G. (2004) Structural mechanism of the simultaneous binding of two drugs to a multidrug-binding protein. EMBO J. 23, 2923-2930.
29. Alguel, Y., Meng, C., Teran, W., Krell, T., Ramos, J. L., Gallegos, M. T., and Zhang, X. (2007) Crystal structures of multidrug binding protein TtgR in complex with antibiotics and plant antimicrobials. J. Mol. Biol. 369, 829-840.
30. van Veen, H. W., Higgins, C. F., and Konings, W. N. (2001) Molecular basis of multidrug transport by ATP-binding cassette transporters: A proposed two-cylinder engine model. J. Mol. Microbiol. Biotechnol. 3, 185-192.
31. Poelarends, G. J., and Konings, W. N. (2002) The transmembrane domains of the ABC multidrug transporter LmrA form a cytoplasmic exposed, aqueous chamber within the membrane. J. Biol. Chem. 277, 42891-42898.
32. Loo, T. W., and Clarke, D. M. (1999) The transmembrane domains of the human multidrug resistance P-glycoprotein are sufficient to mediate drug binding and trafficking to the cell surface. J. Biol. Chem. 274, 24759-24765.
33. Ueda, K., Taguchi, Y., and Morishima, M. (1997) How does P-glycoprotein recognize its substrates? Semin. Cancer Biol. 8, 151-159.
34. Kwan, T., Loughrey, H., Brault, M., Gruenheid, S., Urbatsch, I. L., Senior, A. E., and Gros, P. (2000) Functional analysis of a tryptophan-less P-glycoprotein: A tool for tryptophan insertion and fluorescence spectroscopy. Mol. Pharmacol. 58, 37-47.
35. Davis, S. J., Davies, E. A., Tucknott, M. G., Jones, E. Y., and van der Merwe, P. A. (1998) The role of charged residues mediating low affinity protein-protein recognition at the cell surface by CD2. Proc. Natl. Acad. Sci. U.S.A. 95, 5490-5494.
36. Lewinson, O., and Bibi, E. (2001) Evidence for simultaneous binding of dissimilar substrates by the Escherichia coli multidrug transporter MdfA. Biochemistry 40, 12612-12618.