title: How does P-glycoprotein recognize its substrates?
abstract: We review how P-glycoprotein recognizes a wide variety of compounds and how it carries its substrates across membranes. Amino acid substitutions that affect the substrate specificity of P-glycoprotein have been found scattered throughout the molecule. In particular, some amino acid residues in the putative transmembrane domain (TM) 1 together with TM5-6 and TM11-12 may help to govern substrate specificity. The features that substrates for P-glycoprotein share are also discussed. The amphipathy of a substrate may decide whether the substrate can be intercalated into the lipid bilayer of the membrane. In addition, only certain molecular volumes and tertiary structures may make it possible for the substrate to fit into the substrate-binding site(s) of P-glycoprotein.
authors.affiliation: Laboratory of Biochemistry, Graduate School of Agriculture, Kyoto University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ueda
authors.forename: Y
authors.initials: Y
authors.lastname: Taguchi
authors.forename: M
authors.initials: M
authors.lastname: Morishima
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004252:DNA Mutational Analysis; D006801:Humans; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D011993:Recombinant Fusion Proteins