PMID:12738864
| Citation |
Yu, EW, McDermott, G, Zgurskaya, HI, Nikaido, H and Koshland, DE Jr (2003) Structural basis of multiple drug-binding capacity of the AcrB multidrug efflux pump. Science 300:976-80 |
|---|---|
| Abstract |
Multidrug efflux pumps cause serious problems in cancer chemotherapy and treatment of bacterial infections. Yet high-resolution structures of ligand transporter complexes have previously been unavailable. We obtained x-ray crystallographic structures of the trimeric AcrB pump from Escherichia coli with four structurally diverse ligands. The structures show that three molecules of ligands bind simultaneously to the extremely large central cavity of 5000 cubic angstroms, primarily by hydrophobic, aromatic stacking and van der Waals interactions. Each ligand uses a slightly different subset of AcrB residues for binding. The bound ligand molecules often interact with each other, stabilizing the binding. |
| Links |
PubMed Online version:10.1126/science.1083137 |
| Keywords |
Anti-Infective Agents/chemistry; Anti-Infective Agents/metabolism; Anti-Infective Agents, Local/chemistry; Anti-Infective Agents, Local/metabolism; Binding Sites; Carrier Proteins/chemistry; Carrier Proteins/isolation & purification; Carrier Proteins/metabolism; Cell Membrane/chemistry; Chemistry, Physical; Ciprofloxacin/chemistry; Ciprofloxacin/metabolism; Crystallization; Crystallography, X-Ray; Dequalinium/chemistry; Dequalinium/metabolism; Escherichia coli Proteins/chemistry; Escherichia coli Proteins/isolation & purification; Escherichia coli Proteins/metabolism; Ethidium/chemistry; Ethidium/metabolism; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Ligands; Membrane Proteins/chemistry; Membrane Proteins/isolation & purification; Membrane Proteins/metabolism; Models, Molecular; Multidrug Resistance-Associated Proteins; Physicochemical Phenomena; Protein Binding; Protein Conformation; Protein Structure, Quaternary; Protein Structure, Secondary; Protein Structure, Tertiary; Rhodamines/chemistry; Rhodamines/metabolism; Static Electricity |
| edit table |
Significance
You can help EcoliWiki by summarizing why this paper is useful
Useful Materials and Methods
You can help Ecoliwiki by describing the useful materials (strains, plasmids, antibodies, etc) described in this paper.
Annotations
<annotationlinks/>
EcoliWiki Links
Add links to pages that link here (e.g. gene, product, method pages)
References
See Help:References for how to manage references in EcoliWiki.