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J. Mol. Micro. Biotechnol. 3: 185-192
Molecular Basis of Multidrug Transport by ATP-Binding Cassette Transporters: A Proposed Two-Cylinder Engine Model
Hendrik W. van Veen, Christopher F. Higgins, and Wil N. Konings
ATP-binding cassette multidrug transporters are probably present in all living cells, and are able to export
a variety of structurally unrelated compounds at the expense of ATP hydrolysis. The elevated expression
of these proteins in multidrug resistant cells interferes with the drug-based control of cancers and
infectious pathogenic microorganisms. Multidrug transporters interact directly with the drug substrates. Insights into
the structural elements in drug molecules and transport proteins that are required for this interaction are
now beginning to emerge. However, much remains to be learned about the nature and number of drug binding
sites in the transporters, and the mechanism(s) by which ATP hydrolysis is coupled to changes in affinity
and/or accessibility of drug binding sites. This review summarizes recent advances in answering these questions
for the human multidrug resistance P-glycoprotein and its prokaryotic homolog LmrA. The relevance of
these findings for other ATP-binding cassette transporters will be discussed.
Full article [pdf]
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