The catalytic cycle of P-glycoprotein

FEBS Lett. 1995 Dec 27;377(3):285-9. doi: 10.1016/0014-5793(95)01345-8.


P-glycoprotein is a plasma-membrane glycoprotein which confers multidrug-resistance on cells and displays ATP-driven drug-pumping in vitro. It contains two nucleotide-binding domains, and its structure places it in the 'ABC transporter' family. We review recent evidence that both nucleotide-sites bind and hydrolyse Mg-ATP. The two catalytic sites interact strongly. A minimal scheme for the MgATP hydrolysis reaction is presented. An alternating catalytic sites scheme is proposed, in which drug transport is coupled to relaxation of a high-energy catalytic site conformation generated by the hydrolysis step. Other ABC transporters may show similar catalytic features.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Adenosine Triphosphatases / metabolism*
  • Adenosine Triphosphate / metabolism*
  • Binding Sites
  • Biological Transport
  • Drug Resistance, Multiple / physiology*


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