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Updated: Jul 28, 2026
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Expression, Detergent Solubilization, and Purification of a Membrane Transporter, the MexB Multidrug Resistance Protein
Published on: December 3, 2010
A structure-based mechanism for drug binding by multidrug transporters
E E Zheleznova1, P Markham, R Edgar
1Dept of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland, OR, USA.
Trends in Biochemical Sciences
|February 9, 2000
Summary
Multidrug transporters bind drugs via a mechanism involving conformational changes. This exposes a charged residue, allowing only complementary drugs to bind within the transporter.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Multidrug transporters are crucial for cellular defense, removing diverse cytotoxic compounds.
- The precise mechanisms of substrate binding and translocation by these transporters remain largely unknown.
- Understanding transporter function is vital for combating drug resistance and improving therapeutic outcomes.
Purpose of the Study:
- To elucidate the binding mechanism of cationic lipophilic drugs by multidrug transporters.
- To propose a molecular model for drug recognition and entry into the transporter.
- To investigate the role of specific residues and conformational changes in substrate binding.
Main Methods:
- Analysis of crystal structures of the multidrug-binding domain of transcription activator BmrR.
- Site-directed mutagenesis studies on the bacterial multidrug transporter MdfA.
- Computational modeling and structural analysis of drug-transporter interactions.
Main Results:
- A proposed mechanism involving a conformational change in the transporter.
- Identification of a buried charged residue within the substrate-binding pocket.
- Demonstration that drug binding is dependent on steric and electrostatic complementarity.
- Structural insights into how transporters accommodate chemically diverse substrates.
Conclusions:
- Multidrug transporters utilize a conformational mechanism to selectively bind drugs.
- A buried charged residue plays a key role in substrate recognition.
- The proposed mechanism provides a framework for understanding multidrug transporter function and substrate specificity.
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