|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Structures of the multidrug exporter AcrB reveal a proximal multisite drug-binding pocket== | | ==Structures of the multidrug exporter AcrB reveal a proximal multisite drug-binding pocket== |
| - | <StructureSection load='3aoa' size='340' side='right' caption='[[3aoa]], [[Resolution|resolution]] 3.35Å' scene=''> | + | <StructureSection load='3aoa' size='340' side='right'caption='[[3aoa]], [[Resolution|resolution]] 3.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3aoa]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3AOA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3AOA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3aoa]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3AOA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3AOA FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">acrB, acrE, b0462, EcDH1_3148, JW0451 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">acrB, acrE, b0462, EcDH1_3148, JW0451 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3aoa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3aoa OCA], [http://pdbe.org/3aoa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3aoa RCSB], [http://www.ebi.ac.uk/pdbsum/3aoa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3aoa ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3aoa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3aoa OCA], [https://pdbe.org/3aoa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3aoa RCSB], [https://www.ebi.ac.uk/pdbsum/3aoa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3aoa ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ACRB_ECOLI ACRB_ECOLI]] AcrAB is a drug efflux protein with a broad substrate specificity.<ref>PMID:16915237</ref> <ref>PMID:16946072</ref> <ref>PMID:17194213</ref> | + | [[https://www.uniprot.org/uniprot/ACRB_ECOLI ACRB_ECOLI]] AcrAB is a drug efflux protein with a broad substrate specificity.<ref>PMID:16915237</ref> <ref>PMID:16946072</ref> <ref>PMID:17194213</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 23: |
Line 23: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Ecoli]] | | [[Category: Ecoli]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Nakashima, R]] | | [[Category: Nakashima, R]] |
| | [[Category: Sakurai, K]] | | [[Category: Sakurai, K]] |
| Structural highlights
Function
[ACRB_ECOLI] AcrAB is a drug efflux protein with a broad substrate specificity.[1] [2] [3]
Publication Abstract from PubMed
AcrB and its homologues are the principal multidrug transporters in Gram-negative bacteria and are important in antibiotic drug tolerance. AcrB is a homotrimer that acts as a tripartite complex with the outer membrane channel TolC and the membrane fusion protein AcrA. Minocycline and doxorubicin have been shown to bind to the phenylalanine cluster region of the binding monomer. Here we report the crystal structures of AcrB bound to the high-molecular-mass drugs rifampicin and erythromycin. These drugs bind to the access monomer, and the binding sites are located in the proximal multisite binding pocket, which is separated from the phenylalanine cluster region (distal pocket) by the Phe-617 loop. Our structures indicate that there are two discrete multisite binding pockets along the intramolecular channel. High-molecular-mass drugs first bind to the proximal pocket in the access state and are then forced into the distal pocket in the binding state by a peristaltic mechanism involving subdomain movements that include a shift of the Phe-617 loop. By contrast, low-molecular-mass drugs, such as minocycline and doxorubicin, travel through the proximal pocket without specific binding and immediately bind to the distal pocket. The presence of two discrete, high-volume multisite binding pockets contributes to the remarkably broad substrate recognition of AcrB.
Structures of the multidrug exporter AcrB reveal a proximal multisite drug-binding pocket.,Nakashima R, Sakurai K, Yamasaki S, Nishino K, Yamaguchi A Nature. 2011 Nov 27;480(7378):565-9. doi: 10.1038/nature10641. PMID:22121023[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Murakami S, Nakashima R, Yamashita E, Matsumoto T, Yamaguchi A. Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature. 2006 Sep 14;443(7108):173-9. Epub 2006 Aug 16. PMID:16915237 doi:10.1038/nature05076
- ↑ Seeger MA, Schiefner A, Eicher T, Verrey F, Diederichs K, Pos KM. Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism. Science. 2006 Sep 1;313(5791):1295-8. PMID:16946072 doi:313/5791/1295
- ↑ Sennhauser G, Amstutz P, Briand C, Storchenegger O, Grutter MG. Drug export pathway of multidrug exporter AcrB revealed by DARPin inhibitors. PLoS Biol. 2007 Jan;5(1):e7. PMID:17194213 doi:10.1371/journal.pbio.0050007
- ↑ Nakashima R, Sakurai K, Yamasaki S, Nishino K, Yamaguchi A. Structures of the multidrug exporter AcrB reveal a proximal multisite drug-binding pocket. Nature. 2011 Nov 27;480(7378):565-9. doi: 10.1038/nature10641. PMID:22121023 doi:10.1038/nature10641
|
