title: Towards understanding promiscuity in multidrug efflux pumps.
abstract: Drug export from cells is a major factor in the acquisition of cellular resistance to antimicrobial and cancer chemotherapy, and poses a significant threat to future clinical management of disease. Many of the proteins that catalyse drug efflux do so with remarkably low substrate specificity, a phenomenon known as multidrug transport. For these reasons we need a greater understanding of drug recognition and transport in multidrug pumps to inform research that attempts to circumvent their action. Structural and computational studies have been heralded as being great strides towards a full elucidation of multidrug recognition and transport. In this review we summarise these advances and ask how close we are to a molecular understanding of this remarkable phenomenon.
authors: School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK.
authors: Kelvin
authors: K
authors: Wong
authors: Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
authors: Jerome
authors: J
authors: Ma
authors: Life & Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, UK.
authors: Alice
authors: A
authors: Rothnie
authors: Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
authors: Philip C
authors: PC
authors: Biggin
authors: School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK. Electronic address: ian.Kerr@nottingham.ac.uk.
authors: Ian D
authors: ID
authors: Kerr
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D001692:Biological Transport; D024881:Drug Resistance, Bacterial; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D018528:ATP-Binding Cassette Transporters; D001425:Bacterial Outer Membrane Proteins
keywords: ABC transporter; MATE transporter; MFS transporter; P-glycoprotein.; RND transporter; SMR transporter; antibiotic resistance; chemotherapy; drug resistance