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4dx7

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==Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop==
==Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop==
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<StructureSection load='4dx7' size='340' side='right' caption='[[4dx7]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
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<StructureSection load='4dx7' size='340' side='right'caption='[[4dx7]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4dx7]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DX7 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4dx7]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DX7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DX7 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D10:DECANE'>D10</scene>, <scene name='pdbligand=D12:DODECANE'>D12</scene>, <scene name='pdbligand=DM2:DOXORUBICIN'>DM2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEX:HEXANE'>HEX</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=LMU:DODECYL-ALPHA-D-MALTOSIDE'>LMU</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.253&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dx5|4dx5]], [[4dx6|4dx6]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D10:DECANE'>D10</scene>, <scene name='pdbligand=D12:DODECANE'>D12</scene>, <scene name='pdbligand=DM2:DOXORUBICIN'>DM2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEX:HEXANE'>HEX</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=LMU:DODECYL-ALPHA-D-MALTOSIDE'>LMU</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">acrB, acrE, b0462, JW0451 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4dx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dx7 OCA], [https://pdbe.org/4dx7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dx7 RCSB], [https://www.ebi.ac.uk/pdbsum/4dx7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dx7 ProSAT]</span></td></tr>
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<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=4dx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dx7 OCA], [http://pdbe.org/4dx7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dx7 RCSB], [http://www.ebi.ac.uk/pdbsum/4dx7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dx7 ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[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>
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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AcrAB-TolC is the major efflux protein complex in Escherichia coli extruding a vast variety of antimicrobial agents from the cell. The inner membrane component AcrB is a homotrimer, and it has been postulated that the monomers cycle consecutively through three conformational stages designated loose (L), tight (T), and open (O) in a concerted fashion. Binding of drugs has been shown at a periplasmic deep binding pocket in the T conformation. The initial drug-binding step and transport toward this drug-binding site has been elusive thus far. Here we report high resolution structures (1.9-2.25 A) of AcrB/designed ankyrin repeat protein (DARPin) complexes with bound minocycline or doxorubicin. In the AcrB/doxorubicin cocrystal structure, binding of three doxorubicin molecules is apparent, with one doxorubicin molecule bound in the deep binding pocket of the T monomer and two doxorubicin molecules in a stacked sandwich arrangement in an access pocket at the lateral periplasmic cleft of the L monomer. This access pocket is separated from the deep binding pocket apparent in the T monomer by a switch-loop. The localization and conformational flexibility of this loop seems to be important for large substrates, because a G616N AcrB variant deficient in macrolide transport exhibits an altered conformation within this loop region. Transport seems to be a stepwise process of initial drug uptake in the access pocket of the L monomer and subsequent accommodation of the drug in the deep binding pocket during the L to T transition to the internal deep binding pocket of the T monomer.
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Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop.,Eicher T, Cha HJ, Seeger MA, Brandstatter L, El-Delik J, Bohnert JA, Kern WV, Verrey F, Grutter MG, Diederichs K, Pos KM Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5687-92. Epub 2012 Mar 26. PMID:22451937<ref>PMID:22451937</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4dx7" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Ecoli]]
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[[Category: Escherichia coli K-12]]
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[[Category: Synthetic construct sequences]]
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[[Category: Large Structures]]
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[[Category: Bohnert, J A]]
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[[Category: Synthetic construct]]
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[[Category: Brandstaetter, L]]
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[[Category: Bohnert JA]]
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[[Category: Cha, H]]
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[[Category: Brandstaetter L]]
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[[Category: Diederichs, K]]
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[[Category: Cha H]]
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[[Category: Eicher, T]]
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[[Category: Diederichs K]]
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[[Category: El-Delik, J]]
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[[Category: Eicher T]]
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[[Category: Gruetter, M G]]
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[[Category: El-Delik J]]
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[[Category: Kern, W V]]
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[[Category: Gruetter MG]]
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[[Category: Pos, K M]]
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[[Category: Kern WV]]
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[[Category: Seeger, M A]]
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[[Category: Pos KM]]
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[[Category: Verrey, F]]
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[[Category: Seeger MA]]
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[[Category: Darpin]]
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[[Category: Verrey F]]
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[[Category: Membrane protein]]
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[[Category: Multidrug efflux protein]]
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[[Category: Transport protein]]
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Current revision

Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop

PDB ID 4dx7

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