title: New substrates on the block: clinically relevant resistances for EmrE and homologues.
abstract: Transporters of the small multidrug resistance (SMR) family are small homo- or heterodimers that confer resistance to multiple toxic compounds by exchanging substrate with protons. Despite the wealth of biochemical information on EmrE, the most studied SMR member, a high-resolution three-dimensional structure is missing. To provide proteins that are more amenable to biophysical and structural studies, we identified and partially characterized SMR transporters from bacteria living under extreme conditions of temperature and radiation. Interestingly, these homologues as well as EmrE confer resistance to streptomycin and tobramycin, two aminoglycoside antibiotics widely used in clinics. These are hydrophilic and clinically important substrates of SMRs, and study of their mode of action should contribute to understanding the mechanism of transport and to combating the phenomenon of multidrug resistance. Furthermore, our study of one of the homologues, a putative heterodimer, supports the suggestion that in the SMR family, heterodimers can also function as homodimers.
authors.affiliation: Department of Biological Chemistry, Alexander A Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Nasie
authors.forename: Sonia
authors.initials: S
authors.lastname: Steiner-Mordoch
authors.forename: Shimon
authors.initials: S
authors.lastname: Schuldiner
mesh_terms: D000595:Amino Acid Sequence; D017920:Antiporters / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D034301:Deinococcus / Q000187:drug effects / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment; D013307:Streptomycin / Q000494:pharmacology; D014031:Tobramycin / Q000494:pharmacology
chemical_list: D017920:Antiporters; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D013307:Streptomycin; D014031:Tobramycin; C075436:EmrE protein, E coli