View source for 3aob


==Structures of the multidrug exporter AcrB reveal a proximal multisite drug-binding pocket==
<StructureSection load='3aob' size='340' side='right'caption='[[3aob]], [[Resolution|resolution]] 3.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3aob]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3AOB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3AOB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RFP:RIFAMPICIN'>RFP</scene></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=3aob FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3aob OCA], [https://pdbe.org/3aob PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3aob RCSB], [https://www.ebi.ac.uk/pdbsum/3aob PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3aob ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== 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<ref>PMID:22121023</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3aob" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Nakashima R]]
[[Category: Sakurai K]]
[[Category: Yamaguchi A]]