The catalytic cycle of P-glycoprotein.

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Senior AE, al-Shawi MK, Urbatsch IL

The catalytic cycle of P-glycoprotein.

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

PubMed ID

8549739 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Concanamycin A	P-glycoprotein 1	Protein	Humans	Yes	Inhibitor	Details