Specificity determinants in small multidrug transporters

Journal of Molecular Biology

Volumn 427, Issue 2, 2015, Pages 468-477

  Brill, Shlomo ^a   Sade Falk, Ofir ^a,b   Elbaz Alon, Yael ^a,c   Schuldiner, Shimon ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^b BEN GURION UNIVERSITY OF THE NEGEV   (Israel)

^c WEIZMANN INSTITUTE OF SCIENCE   (Israel)

Author keywords

Antibiotic resistance; EmrE; Ion coupled antiporters; Methyl viologen; Multidrug transporters

Indexed keywords

MULTIDRUG RESISTANCE PROTEIN; PARAQUAT; PROTEOLIPOSOME; SERINE; SERINE43; UNCLASSIFIED DRUG; ANTIPORTER; EMRE PROTEIN, E COLI; ESCHERICHIA COLI PROTEIN;

ANTIBIOTIC RESISTANCE; ARTICLE; BINDING SITE; BORDETELLA PERTUSSIS; DRUG BINDING; DRUG MECHANISM; ENZYME SPECIFICITY; ESCHERICHIA COLI; IN VITRO STUDY; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PRIORITY JOURNAL; SEQUENCE ALIGNMENT; SERRATIA MARCESCENS; THERMOBIFIDA FUSCA; AMINO ACID SEQUENCE; BACILLUS; CHEMICAL STRUCTURE; GENETICS; METABOLISM; MOLECULAR CLONING; MOLECULAR GENETICS; MULTIDRUG RESISTANCE; MUTATION; PLASMID; SENSITIVITY AND SPECIFICITY; TRANSPORT AT THE CELLULAR LEVEL;

BORDETELLA PERTUSSIS; ESCHERICHIA COLI; MYCOBACTERIUM TUBERCULOSIS;

AMINO ACID SEQUENCE; ANTIPORTERS; BACILLUS; BIOLOGICAL TRANSPORT; CLONING, MOLECULAR; DRUG RESISTANCE, MULTIPLE, BACTERIAL; ESCHERICHIA COLI; ESCHERICHIA COLI PROTEINS; MOLECULAR SEQUENCE DATA; MOLECULAR STRUCTURE; MUTATION; MYCOBACTERIUM TUBERCULOSIS; PLASMIDS; SENSITIVITY AND SPECIFICITY; SEQUENCE ALIGNMENT;

EID: 84920774000     PISSN: 00222836     EISSN: 10898638     Source Type: Journal    
DOI: 10.1016/j.jmb.2014.11.015     Document Type: Article

References (40)

1. Bush K, Courvalin P, Dantas G, Davies J, Eisenstein B, Huovinen P, et al. Tackling antibiotic resistance. Nat Rev Microbiol 2011;9:894-6.
2. Center for Disease Control. Antibiotics resistance threats in the USA, 2013. Annual Report of the CDC. USA: Centers for Disease Control; 2013.
3. Organization WWH. Antimicrobial resistance: global report on surveillance; 2014.
4. Piddock LJ. Multidrug-resistance efflux pumps-not just for resistance. Nat Rev Microbiol 2006;4:629-36.
5. Nikaido H, Pages JM. Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria. FEMS Microbiol Rev 2012;36:340-63.
6. Lomovskaya O, Zgurskaya HI, Totrov M, Watkins WJ. Waltzing transporters and "the dance macabre" between humans and bacteria. Nat Rev Drug Discov 2007;6:56-65.
7. Fluman N, Bibi E. Bacterial multidrug transport through the lens of the major facilitator superfamily. Biochim Biophys Acta 2009; 1794:738-47.
8. Schuldiner S. EmrE, a model for studying evolution and mechanism of ion-coupled transporters. Biochim Biophys Acta 2009;1794:748-62.
9. Omote H, Hiasa M, Matsumoto T, Otsuka M, Moriyama Y. The MATE proteins as fundamental transporters of metabolic and xenobiotic organic cations. Trends Pharmacol Sci 2006;27:587-93.
10. Murakami S, Yamaguchi A. Multidrug-exporting secondary transporters. Curr Opin Struct Biol 2003;13:443-52.
11. Pos KM. Drug transport mechanism of the AcrB efflux pump. Biochim Biophys Acta 2009;1794:782-93.
12. Wong K, Ma J, Rothnie A, Biggin PC, Kerr ID. Towards understanding promiscuity in multidrug efflux pumps. Trends Biochem Sci 2014;39:8-16.
13. Nikaido H. Multidrug resistance in bacteria. Annu Rev Biochem 2009;78:119-46.
14. Tal N, Schuldiner S. A coordinated network of transporters with overlapping specificities provides a robust survival strategy. Proc Natl Acad Sci USA 2009;106:9051-6.
15. Schuldiner S. What Can a Living Fossil Tell Us About Evolution and Mechanism of Ion-Coupled Transporters: The Story of Small Multidrug Transporters. In: Krämer R, editor. Ziegler C, editors. Membrane Transport Mechanism: Springer Berlin Heidelberg; 2014. p. 233-48.
16. Yerushalmi H, Lebendiker M, Schuldiner S. EmrE, an Escherichia coli 12-kDa multidrug transporter, exchanges toxic cations and H+ and is soluble in organic solvents. J Biol Chem 1995;270:6856-63.
17. + antiporter gene of Escherichia coli. Proc Natl Acad Sci USA 1987;84:2615-9.
18. Tabor S, Richardson C. A bacteriophage T7 RNA polymerase/promoter system for controlled exclusive expression of specific genes. Proc Natl Acad Sci USA 1985;82:1074-8.
19. Muth TR, Schuldiner S. A membrane-embedded glutamate is required for ligand binding to the multidrug transporter EmrE. EMBO J 2000;19:234-40.
20. Ninio S, Rotem D, Schuldiner S. Functional analysis of novel multidrug transporters from human pathogens. J Biol Chem 2001;276:48250-6.
21. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997; 25:3389-402.
22. Crooks GE, Hon G, Chandonia JM, Brenner SE. WebLogo: a sequence logo generator. Genome Res 2004;14:1188-90.
23. Schneider TD, Stephens RM. Sequence logos: a new way to display consensus sequences. Nucleic Acids Res 1990;18:6097-100.
24. Li F, Mullins JI. Site-directed mutagenesis facilitated by DpnI selection on hemimethylated DNA. Methods Mol Biol 2002;182:19-27.
25. Brill S, Falk OS, Schuldiner S. Transforming a drug/H+ antiporter into a polyamine importer by a single mutation. Proc Natl Acad Sci USA 2012;109:16894-9.
26. Yerushalmi H, Mordoch SS, Schuldiner S. A single carboxyl mutant of the multidrug transporter EmrE is fully functional. J Biol Chem 2001;276:12744-8.
27. Minato Y, Shahcheraghi F, Ogawa W, Kuroda T, Tsuchiya T. Functional gene cloning and characterization of the SsmE multidrug efflux pump from Serratia marcescens. Biol Pharm Bull 2008;31:516-9.
28. Ninio S, Schuldiner S. Characterization of an archaeal multidrug transporter with a unique amino acid composition. J Biol Chem 2003;278:12000-5.
29. Nasie I, Steiner-Mordoch S, Schuldiner S. New substrates on the block: clinically relevant resistances for EmrE and homologues. J Bacteriol 2012;194:6766-70.
30. +-coupled multidrug transporter from Escherichia coli, reveals a hydrophobic pathway for solutes. J Biol Chem 1999;274:19480-6.
31. Rotem D, Steiner-Mordoch S, Schuldiner S. Identification of tyrosine residues critical for the function of an ion-coupled multidrug transporter. J Biol Chem 2006;281:18715-22.
32. Srinivasan VB, Rajamohan G, Gebreyes WA. Role of AbeS, a novel efflux pump of the SMR family of transporters, in resistance to antimicrobial agents in Acinetobacter baumannii. Antimicrob Agents Chemother 2009;53:5312-6.
33. Chen YJ, Pornillos O, Lieu S, Ma C, Chen AP, Chang G. X-ray structure of EmrE supports dual topology model. Proc Natl Acad Sci USA 2007;104:18999-9004.
34. Fleishman SJ, Harrington SE, Enosh A, Halperin D, Tate CG, Ben-Tal N. Quasi-symmetry in the cryo-EM structure of EmrE provides the key tomodeling its transmembrane domain. J Mol Biol 2006;364:54-67.
35. Schuldiner S. Undecided membrane proteins insert in random topologies. Up, down and sideways: it does not really matter. Trends Biochem Sci 2012;37:215-9.
36. Jack DL, Storms ML, Tchieu JH, Paulsen IT, Saier MH. A broad-specificity multidrug efflux pump requiring a pair of homologous SMR-type proteins. J Bacteriol 2000;182:2311-3.
37. Neyfakh AA. Mystery of multidrug transporters: the answer can be simple. Mol Microbiol 2002;44:1123-30.
38. Nakashima R, Sakurai K, Yamasaki S, Hayashi K, Nagata C, Hoshino K, et al. Structural basis for the inhibition of bacterial multidrug exporters. Nature 2013;500:102-6.
39. Eicher T, Cha HJ, Seeger MA, Brandstatter L, El-Delik J, Bohnert JA, et al. Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop. Proc Natl Acad Sci USA 2012;109:5687-92.
40. Peters KM, Brooks BE, Schumacher MA, Skurray RA, Brennan RG, Brown MH. A single acidic residue can guide binding site selection but does not govern QacR cationic-drug affinity. PLoS One 2011;6:e15974.