2j8s: Difference between revisions

Latest revision as of 14:38, 13 December 2023

Drug Export Pathway of Multidrug Exporter AcrB Revealed by DARPin Inhibitors

Structural highlights

2j8s is a 5 chain structure with sequence from Escherichia coli K-12 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.54Å
Ligands:	LMT, LMU
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ACRB_ECOLI AcrAB is a drug efflux protein with a broad substrate specificity.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The multidrug exporter AcrB is the inner membrane component of the AcrAB-TolC drug efflux system in Escherichia coli and is responsible for the resistance of this organism to a wide range of drugs. Here we describe the crystal structure of the trimeric AcrB in complex with a designed ankyrin-repeat protein (DARPin) inhibitor at 2.5-A resolution. The three subunits of AcrB are locked in different conformations revealing distinct channels in each subunit. There seems to be remote conformational coupling between the channel access, exit, and the putative proton-translocation site, explaining how the proton motive force is used for drug export. Thus our structure suggests a transport pathway not through the central pore but through the identified channels in the individual subunits, which greatly advances our understanding of the multidrug export mechanism.

Drug export pathway of multidrug exporter AcrB revealed by DARPin inhibitors.,Sennhauser G, Amstutz P, Briand C, Storchenegger O, Grutter MG PLoS Biol. 2007 Jan;5(1):e7. PMID:17194213^[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
↑ 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

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] 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

[4] 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

[1]

[2]

[3]

[4]

@@ Line 3: / Line 3: @@
 <StructureSection load='2j8s' size='340' side='right'caption='[[2j8s]], [[Resolution|resolution]] 2.54&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2j8s]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Ecoli Ecoli] and [https://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=2J8S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J8S FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2j8s]] 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=2J8S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J8S FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=LMU:DODECYL-ALPHA-D-MALTOSIDE'>LMU</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.54&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1iwg|1iwg]], [[1oy6|1oy6]], [[1oy8|1oy8]], [[1oy9|1oy9]], [[1oyd|1oyd]], [[1oye|1oye]], [[1t9t|1t9t]], [[1t9u|1t9u]], [[1t9v|1t9v]], [[1t9w|1t9w]], [[1t9x|1t9x]], [[1t9y|1t9y]], [[2gif|2gif]], [[2hrt|2hrt]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=LMU:DODECYL-ALPHA-D-MALTOSIDE'>LMU</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=2j8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j8s OCA], [https://pdbe.org/2j8s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j8s RCSB], [https://www.ebi.ac.uk/pdbsum/2j8s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j8s 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>
+[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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 33: @@
 __TOC__
 </StructureSection>
-[[Category: Ecoli]]
+[[Category: Escherichia coli K-12]]
 [[Category: Large Structures]]
-[[Category: Synthetic construct sequences]]
+[[Category: Synthetic construct]]
-[[Category: Amstutz, P]]
+[[Category: Amstutz P]]
-[[Category: Briand, C]]
+[[Category: Briand C]]
-[[Category: Gruetter, M G]]
+[[Category: Gruetter MG]]
-[[Category: Sennhauser, G]]
+[[Category: Sennhauser G]]
-[[Category: Storchenegger, O]]
+[[Category: Storchenegger O]]
-[[Category: Antibiotic resistance]]
-[[Category: Antibiotic resistance-inhibitor complex]]
-[[Category: Co-crystallization]]
-[[Category: Designed ankyrin repeat protein]]
-[[Category: Drug-efflux pump]]
-[[Category: Inhibitor]]
-[[Category: Inner membrane]]
-[[Category: Membrane]]
-[[Category: Membrane protein]]
-[[Category: Membrane protein-complex]]
-[[Category: Multidrug resistance protein]]
-[[Category: Protein complex]]
-[[Category: Rnd]]
-[[Category: Transmembrane]]
-[[Category: Transport]]
-[[Category: Transport protein]]

2j8s: Difference between revisions

Latest revision as of 14:38, 13 December 2023

Drug Export Pathway of Multidrug Exporter AcrB Revealed by DARPin Inhibitors

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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