View source for 7oul


==BDM88832 inhibitor bound to the transmembrane domain of AcrB-R971A==
<StructureSection load='7oul' size='340' side='right'caption='[[7oul]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7oul]] 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=7OUL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OUL 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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1KE:1-(3-chloranyl-5-iodanyl-pyridin-2-yl)piperazine'>1KE</scene>, <scene name='pdbligand=C14:TETRADECANE'>C14</scene>, <scene name='pdbligand=D12:DODECANE'>D12</scene>, <scene name='pdbligand=DDQ:DECYLAMINE-N,N-DIMETHYL-N-OXIDE'>DDQ</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=LPX:(2S)-3-{[(R)-(2-AMINOETHOXY)(HYDROXY)PHOSPHORYL]OXY}-2-HYDROXYPROPYL+HEXADECANOATE'>LPX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7oul FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oul OCA], [https://pdbe.org/7oul PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oul RCSB], [https://www.ebi.ac.uk/pdbsum/7oul PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oul 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 ==
Efflux transporters of the RND family confer resistance to multiple antibiotics in Gram-negative bacteria. Here, we identify and chemically optimize pyridylpiperazine-based compounds that potentiate antibiotic activity in E. coli through inhibition of its primary RND transporter, AcrAB-TolC. Characterisation of resistant E. coli mutants and structural biology analyses indicate that the compounds bind to a unique site on the transmembrane domain of the AcrB L protomer, lined by key catalytic residues involved in proton relay. Molecular dynamics simulations suggest that the inhibitors access this binding pocket from the cytoplasm via a channel exclusively present in the AcrB L protomer. Thus, our work unveils a class of allosteric efflux-pump inhibitors that likely act by preventing the functional catalytic cycle of the RND pump.

Pyridylpiperazine-based allosteric inhibitors of RND-type multidrug efflux pumps.,Ple C, Tam HK, Vieira Da Cruz A, Compagne N, Jimenez-Castellanos JC, Muller RT, Pradel E, Foong WE, Malloci G, Ballee A, Kirchner MA, Moshfegh P, Herledan A, Herrmann A, Deprez B, Willand N, Vargiu AV, Pos KM, Flipo M, Hartkoorn RC Nat Commun. 2022 Jan 10;13(1):115. doi: 10.1038/s41467-021-27726-2. PMID:35013254<ref>PMID:35013254</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7oul" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Foong WE]]
[[Category: Pos KM]]
[[Category: Tam HK]]