title: RND efflux pumps: structural information translated into function and inhibition mechanisms.
abstract: Efflux pumps of the Resistance Nodulation Division (RND) superfamily play a major role in the intrinsic and acquired resistance of Gram-negative pathogens to antibiotics. Moreover, they are largely responsible for multi-drug resistance (MDR) phenomena in these bacteria. The last decade has seen a sharp increase in the number of experimental and computational studies aimed at understanding their functional mechanisms. Most of these studies focused on the RND drug/proton antiporter AcrB, part of the AcrAB-TolC efflux pump actively recognizing and expelling noxious agents from the interior of bacteria. These studies have been focused on the dynamical interactions between AcrB and its substrates and inhibitors, on the details of the proton translocation mechanisms, and on the way AcrB assembles with protein partners to build up a functional pump. In this review we summarize these advances focusing on the role of AcrB.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ruggerone
authors.forename: Satoshi
authors.initials: S
authors.lastname: Murakami
authors.forename: Klaas M
authors.initials: KM
authors.lastname: Pos
authors.affiliation: Department of Physics, University of Cagliari, S.P. 8, km 0.700, 09042 Monserrato (CA), Italy. vargiu@dsf.unica.it.
authors.forename: Attilio V
authors.initials: AV
authors.lastname: Vargiu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000502:physiology; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000502:physiology; D008074:Lipoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008074:Lipoproteins; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C083497:AcrA protein, E coli; C083496:AcrB protein, E coli; C474926:AcrB protein, Salmonella enterica; C073126:tolC protein, E coli