Staphylococcal multidrug efflux protein QacA.
The QacA multidrug exporter from Staphylococcus aureus mediates resistance to a wide array of monovalent or divalent cationic, lipophilic, antimicrobial compounds. QacA provides resistance to these various compounds via a proton motive force-dependent antiport mechanism that conforms to classical Michaelis-Menten kinetics. Fluorescent transport analyses have demonstrated that this QacA:substrate interaction occurs with high affinity and competition studies have shown that QacA-mediated ethidium export is competitively inhibited by other monovalent cations, and non-competitively inhibited by divalent cations, suggesting that monovalent and divalent cations bind at distinct sites on the QacA protein. The closely related export protein QacB, mediates lower levels of resistance to divalent cations, and lacks a high affinity-binding site for divalent cations. The cell membrane has been identified as the origin of QacA-mediated efflux; substrates are bound and expelled from within this hydrophobic environment. Regulation of qacA expression is achieved via the transacting repressor protein, QacR. QacR belongs to the TetR family of transcriptional repressor proteins, which all possess a helix-turn-helix DNA-binding domain at their N-terminal ends, and have highly divergent C-termini postulated to be involved in the binding of inducing compounds. QacR specifically binds to an inverted repeat, IR1, which has been identified as the qacA operator region, and overlaps the identified promoter sequence for qacA. QacR, like the multidrug export protein whose expression it regulates, has been shown to interact directly with a number of structurally-dissimilar compounds.
Brown
M H
MH
School of Biological Sciences, University of Sydney, New South Wales, Australia.
Skurray
R A
RA
D000588:Amines / Q000493:pharmacokinetics; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D004396:Coloring Agents / Q000493:pharmacokinetics; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D015964:Gene Expression Regulation, Bacterial; D026901:Membrane Transport Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D000644:Quaternary Ammonium Compounds / Q000493:pharmacokinetics; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*
D000588:Amines; D001426:Bacterial Proteins; D002352:Carrier Proteins; D004396:Coloring Agents; D026901:Membrane Transport Proteins; D000644:Quaternary Ammonium Compounds; C068498:qacA protein, Staphylococcus aureus