View source for 6zoh


==3-Formylrifamycin SV binding to the access pocket of AcrB-G619P_G621P L and T protomers==
<StructureSection load='6zoh' size='340' side='right'caption='[[6zoh]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6zoh]] 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=6ZOH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZOH 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=3YI:(2S,12Z,14E,16S,17S,18R,19R,20R,21S,22R,23S,24E)-8-formyl-5,6,9,17,19-pentahydroxy-23-methoxy-2,4,12,16,18,20,22-heptam+ethyl-1,11-dioxo-1,2-dihydro-2,7-(epoxypentadeca[1,11,13]trienoimino)naphtho[2,1-b]furan-21-yl+acetate'>3YI</scene>, <scene name='pdbligand=D10:DECANE'>D10</scene>, <scene name='pdbligand=D12:DODECANE'>D12</scene>, <scene name='pdbligand=DDQ:DECYLAMINE-N,N-DIMETHYL-N-OXIDE'>DDQ</scene>, <scene name='pdbligand=DDR:(2S)-3-HYDROXYPROPANE-1,2-DIYL+DIDECANOATE'>DDR</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=LPX:(2S)-3-{[(R)-(2-AMINOETHOXY)(HYDROXY)PHOSPHORYL]OXY}-2-HYDROXYPROPYL+HEXADECANOATE'>LPX</scene>, <scene name='pdbligand=PTY:PHOSPHATIDYLETHANOLAMINE'>PTY</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=6zoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zoh OCA], [https://pdbe.org/6zoh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zoh RCSB], [https://www.ebi.ac.uk/pdbsum/6zoh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zoh 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 ==
Gram-negative bacteria maintain an intrinsic resistance mechanism against entry of noxious compounds by utilizing highly efficient efflux pumps. The E. coli AcrAB-TolC drug efflux pump contains the inner membrane H(+)/drug antiporter AcrB comprising three functionally interdependent protomers, cycling consecutively through the loose (L), tight (T) and open (O) state during cooperative catalysis. Here, we present 13 X-ray structures of AcrB in intermediate states of the transport cycle. Structure-based mutational analysis combined with drug susceptibility assays indicate that drugs are guided through dedicated transport channels toward the drug binding pockets. A co-structure obtained in the combined presence of erythromycin, linezolid, oxacillin and fusidic acid shows binding of fusidic acid deeply inside the T protomer transmembrane domain. Thiol cross-link substrate protection assays indicate that this transmembrane domain-binding site can also accommodate oxacillin or novobiocin but not erythromycin or linezolid. AcrB-mediated drug transport is suggested to be allosterically modulated in presence of multiple drugs.

Allosteric drug transport mechanism of multidrug transporter AcrB.,Tam HK, Foong WE, Oswald C, Herrmann A, Zeng H, Pos KM Nat Commun. 2021 Jun 29;12(1):3889. doi: 10.1038/s41467-021-24151-3. PMID:34188038<ref>PMID:34188038</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6zoh" 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]]