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The occluded nucleotide conformation of p-glycoprotein
Gregory Tombline1, Alan E Senior
1Department of Biochemistry and Biophysics, University of Rochester Medical Center, Box 712, Rochester, New York 14642, USA.
Abstract:
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.
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