The multi-structural feature of the multidrug resistance gene product P-glycoprotein: implications for its mechanism of action (hypothesis).
P-glycoprotein is a member of the ATP-binding cassette (ABC) transport superfamily. It plays an important role in the development of multidrug resistance in cancers by effluxing a wide variety of anticancer drugs. A large amount of information on the structure and function of P-glycoprotein has been accumulated over recent years from studies using molecular, biochemical, and biophysical approaches. It remains unclear, however, how this protein folds in membranes and how it transports such a wide variety of hydrophobic compounds. This paper highlights the recent progress in the structural and biogenesis aspects of P-glycoprotein. A model mechanism of P-glycoprotein action is proposed as a hypothesis that is based on recent progress in studying the topological folding of P-glycoprotein.
Zhang
J T
JT
Department of Pharmacology and Toxicology, Indiana University Cancer Center and Walther Oncology Institute, Indiana University School of Medicine, Indianapolis 46202, USA. jianzhan@iupui.edu
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry* / Q000502:physiology*; D000818:Animals; D018432:Drug Resistance, Multiple; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1