Recent progress in understanding the mechanism of P-glycoprotein-mediated drug efflux.
P-glycoprotein (P-gp) is an ATP-dependent drug pump that can transport a broad range of hydrophobic compounds out of the cell. The protein is clinically important because of its contribution to the phenomenon of multidrug resistance during AIDS/HIV and cancer chemotherapy. P-gp is a member of the ATP-binding cassette (ABC) family of proteins. It is a single polypeptide that contains two repeats joined by a linker region. Each repeat has a transmembrane domain consisting of six transmembrane segments followed by a hydrophilic domain containing the nucleotide-binding domain. In this mini-review, we discuss recent progress in determining the structure and mechanism of human P-glycoprotein.
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Department of Medicine and Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
Clarke
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D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry* / Q000378:metabolism*; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001693:Biological Transport, Active / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011485:Protein Binding; D013329:Structure-Activity Relationship
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D004364:Pharmaceutical Preparations; D000255:Adenosine Triphosphate