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  • Title: The catalytic cycle of P-glycoprotein.
    Author: Senior AE, al-Shawi MK, Urbatsch IL.
    Journal: FEBS Lett; 1995 Dec 27; 377(3):285-9. PubMed ID: 8549739.
    Abstract:
    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.
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