The occluded nucleotide conformation of p-glycoprotein

J Bioenerg Biomembr. 2005 Dec;37(6):497-500. doi: 10.1007/s10863-005-9498-4.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / chemistry*
  • Adenosine Triphosphate / chemistry
  • Catalysis
  • Dimerization
  • Mutation, Missense
  • Nucleotides / chemistry*
  • Nucleotides / genetics
  • Protein Conformation


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Nucleotides
  • Adenosine Triphosphate