Multiple Molecular Mechanisms for Multidrug Resistance Transporters.
From: MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK. chris.higgins@durham.ac.uk
Nature
- Publish Date: Apr 2007
- ISSN: 1476-4687
- Volume: 446
- Issue: 7137
- Pages: 749-57
- Medium: Internet
- Language: English
- Citation (JAMA): Higgins Christopher F, et al. Multiple Molecular Mechanisms for Multidrug Resistance Transporters.. Nature Apr 2007;446:749-57
Abstract
The acquisition of multidrug resistance is a serious impediment to improved healthcare. Multidrug resistance is most frequently due to active transporters that pump a broad spectrum of chemically distinct, cytotoxic molecules out of cells, including antibiotics, antimalarials, herbicides and cancer chemotherapeutics in humans. The paradigm multidrug transporter, mammalian P-glycoprotein, was identified 30 years ago. Nonetheless, success in overcoming or circumventing multidrug resistance in a clinical setting has been modest. Recent structural and biochemical data for several multidrug transporters now provide mechanistic insights into how they work. Organisms have evolved several elegant solutions to ridding the cell of such cytotoxic compounds. Answers are emerging to questions such as how multispecificity for different drugs is achieved, why multidrug resistance arises so readily, and what chance there is of devising a clinical solution.
Mesh Headings (Keywords): ATP-Binding Cassette Transporters, Animals, Drug Resistance, Multiple, Humans, Multidrug Resistance-Associated Proteins, Protein Conformation, Structure-Activity Relationship, Transcription Factors
Check for Full Text / PubMed Unique Identifier (PMID): 17429392
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