The catalytic cycle of P‐glycoprotein

FEBS Letters - Tập 377 - Trang 285-289 - 1995
Alan E. Senior1, Marwan K. Al-Shawi1, Ina L. Urbatsch1
1Department of Biochemistry, University of Rochester Medical Center, Rochester, NY 14642, USA

Tóm tắt

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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FEBS Letters

Tập 377

285-289

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