The occluded nucleotide conformation of p-glycoprotein.
We review recent work on E552A/E1197A P-glycoprotein. This ATPase-defective mutant occludes MgATP tightly with maximal 1/1 stoichiometry in drug-sensitive fashion. The occluded nucleotide conformation appears to represent a transient, asymmetric, catalytic intermediate. We present a model for catalysis incorporating nucleotide binding domain (NBD) dimerization and the occluded nucleotide conformation, and we speculate as to how catalysis seen in P-glycoprotein might be harmonized with symmetrical dimer structures of isolated NBDs.
Tombline
Gregory
G
Department of Biochemistry and Biophysics, University of Rochester Medical Center, Box 712, Rochester, New York 14642, USA.
Senior
Alan E
AE
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry*; D000255:Adenosine Triphosphate / Q000737:chemistry; D002384:Catalysis; D019281:Dimerization; D020125:Mutation, Missense; D009711:Nucleotides / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009711:Nucleotides; D000255:Adenosine Triphosphate