THE CATALYTIC CYCLE OF P-GLYCOPROTEIN

P-glycoprotein is a plasma-membrane glycoprotein which confers multidr ug-resistance on cells and displays ATP-driven drug-pumping in vitro. It contains two nucleotide-binding domains, and its structure places i t in the 'ABC transporter' family, We review recent evidence that both nucleotide-sites bind and hydrolyse Mg-ATP. The two catalytic sites i nteract strongly, A minimal scheme for the MgATP hydrolysis reaction i s presented. An alternating catalytic sites scheme is proposed, in whi ch drug transport is coupled to relaxation of a high-energy catalytic site conformation generated by the hydrolysis step. Other ABC transpor ters may show similar catalytic features.