Related Experiment Videos
The structure and function of drug pumps: an update
Kenneth S McKeegan1, M Ines Borges-Walmsley, Adrian R Walmsley
1Centre for Infectious Diseases, Wolfson Research Institute, Queen's Campus, University of Durham, Stockton-on-Tees, UK.
Trends in Microbiology
|January 16, 2003
Summary
Recent structural studies of bacterial transporters reveal mechanisms of cellular drug resistance. Advances in understanding multidrug recognition by transcriptional regulators controlling drug pump expression are also highlighted.
Area of Science:
- Biochemistry
- Molecular Biology
- Microbiology
Background:
- Cellular resistance to cytotoxic drugs is often mediated by transmembrane protein pumps.
- Understanding these pumps is crucial for combating drug resistance in various contexts.
- Recent structural biology advancements have shed light on transporter mechanisms.
Purpose of the Study:
- To summarize recent structural insights into bacterial transmembrane protein pumps involved in drug resistance.
- To highlight progress in understanding the molecular basis of multidrug recognition.
- To connect the structure of drug pumps with transcriptional regulators controlling their expression.
Main Methods:
- Determination of the three-dimensional structures of Escherichia coli transporters.
- Structural analysis of transcriptional regulators involved in drug pump regulation.
- Integration of structural data to understand drug-transporter and drug-regulator interactions.
Main Results:
- Structures of three E. coli transporters elucidated: two ATP-binding cassette (ABC) superfamily and one resistance-nodulation-cell division (RND) family.
- Structural information on transcriptional regulators provides insights into binding of structurally unrelated cytotoxic drugs.
- Advances made in understanding the molecular basis of multidrug recognition by these regulators.
Conclusions:
- Recent structural studies have significantly advanced our understanding of drug efflux mechanisms.
- Transcriptional regulators play a key role in multidrug recognition and regulation of drug pump expression.
- Further research into these structures can inform strategies to overcome cellular drug resistance.