Publication Date:
2003-05-10
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Edward W -- McDermott, Gerry -- Zgurskaya, Helen I -- Nikaido, Hiroshi -- Koshland, Daniel E Jr -- AI 09644/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2003 May 9;300(5621):976-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12738864" target="_blank"〉PubMed〈/a〉
Keywords:
Anti-Infective Agents/chemistry/metabolism
;
Anti-Infective Agents, Local/chemistry/metabolism
;
Binding Sites
;
Carrier Proteins/*chemistry/isolation & purification/*metabolism
;
Cell Membrane/chemistry
;
Chemistry, Physical
;
Ciprofloxacin/chemistry/metabolism
;
Crystallization
;
Crystallography, X-Ray
;
Dequalinium/chemistry/metabolism
;
Escherichia coli Proteins/*chemistry/isolation & purification/*metabolism
;
Ethidium/chemistry/metabolism
;
Hydrogen Bonding
;
Hydrophobic and Hydrophilic Interactions
;
Ligands
;
Membrane Proteins/*chemistry/isolation & purification/*metabolism
;
Models, Molecular
;
Multidrug Resistance-Associated Proteins
;
Physicochemical Phenomena
;
Protein Binding
;
Protein Conformation
;
Protein Structure, Quaternary
;
Protein Structure, Secondary
;
Protein Structure, Tertiary
;
Rhodamines/chemistry/metabolism
;
Static Electricity
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
