title: Structure and function of Neisseria gonorrhoeae MtrF illuminates a class of antimetabolite efflux pumps.
abstract: Neisseria gonorrhoeae is an obligate human pathogen and the causative agent of the sexually transmitted disease gonorrhea. The control of this disease has been compromised by the increasing proportion of infections due to antibiotic-resistant strains, which are growing at an alarming rate. N. gonorrhoeae MtrF is an integral membrane protein that belongs to the AbgT family of transporters for which no structural information is available. Here, we describe the crystal structure of MtrF, revealing a dimeric molecule with architecture distinct from all other families of transporters. MtrF is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm to halfway across the membrane bilayer. Each subunit of the transporter contains nine transmembrane helices and two hairpins, posing a plausible pathway for substrate transport. A combination of the crystal structure and biochemical functional assays suggests that MtrF is an antibiotic efflux pump mediating bacterial resistance to sulfonamide antimetabolite drugs.
authors.affiliation: Department of Physics and Astronomy, Iowa State University, Ames, IA 50011, USA.
authors.forename: Chih-Chia
authors.initials: CC
authors.lastname: Su
authors.affiliation: Department of Chemistry, Iowa State University, Ames, IA 50011, USA.
authors.forename: Jani Reddy
authors.initials: JR
authors.lastname: Bolla
authors.affiliation: Department of Chemistry, Iowa State University, Ames, IA 50011, USA.
authors.forename: Nitin
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Department of Chemistry, Iowa State University, Ames, IA 50011, USA.
authors.forename: Abhijith
authors.initials: A
authors.lastname: Radhakrishnan
authors.affiliation: Department of Physics and Astronomy, Iowa State University, Ames, IA 50011, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Long
authors.affiliation: Department of Physics and Astronomy, Iowa State University, Ames, IA 50011, USA.
authors.forename: Jared A
authors.initials: JA
authors.lastname: Delmar
authors.affiliation: Department of Physics and Astronomy, Iowa State University, Ames, IA 50011, USA.
authors.forename: Tsung-Han
authors.initials: TH
authors.lastname: Chou
authors.affiliation: NE-CAT and Department of Chemistry and Chemical Biology, Cornell University, Building 436E, Argonne National Laboratory, 9700 S. Cass Avenue, Argonne, IL 60439, USA.
authors.forename: Kanagalaghatta R
authors.initials: KR
authors.lastname: Rajashankar
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA; Laboratories of Microbial Pathogenesis, VA Medical Center, Decatur, GA 30033, USA; Emory Antibiotic Resistance Center, Emory University, Atlanta, GA 30322, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Shafer
authors.affiliation: Department of Physics and Astronomy, Iowa State University, Ames, IA 50011, USA; Department of Chemistry, Iowa State University, Ames, IA 50011, USA. Electronic address: ewyu@iastate.edu.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Yu
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006069:Gonorrhea / Q000188:drug therapy / Q000235:genetics / Q000382:microbiology*; D006801:Humans; D008958:Models, Molecular; D009344:Neisseria gonorrhoeae / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics; D011487:Protein Conformation; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012097:Repressor Proteins; D013449:Sulfonamides; C087450:mtrR protein, Neisseria gonorrhoeae
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