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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Abbreviations
- Pgp:
-
P-glycoprotein
- NBD:
-
nucleotide binding domain
- TMD:
-
transmembrane domain
- Vi:
-
orthovanadate
- BeFx:
-
beryllium fluoride
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Tombline, G., Senior, A.E. The Occluded Nucleotide Conformation of P-Glycoprotein. J Bioenerg Biomembr 37, 497–500 (2005). https://doi.org/10.1007/s10863-005-9498-4
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DOI: https://doi.org/10.1007/s10863-005-9498-4