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The catalytic cycle of P‐glycoprotein
Author(s) -
Alan E. Senior,
Marwan K. AlShawi,
Ina L. Urbatsch
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)01345-8
Subject(s) - atp hydrolysis , nucleotide , p glycoprotein , chemistry , transporter , atp binding cassette transporter , glycoprotein , hydrolysis , catalysis , catalytic cycle , efflux , biochemistry , in vitro , biophysics , stereochemistry , enzyme , multiple drug resistance , biology , gene , atpase , antibiotics
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.