View source for 7lo7


==NorA in complex with Fab25==
<StructureSection load='7lo7' size='340' side='right'caption='[[7lo7]], [[Resolution|resolution]] 3.74&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7lo7]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LO7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LO7 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.74&#8491;</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=7lo7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lo7 OCA], [https://pdbe.org/7lo7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lo7 RCSB], [https://www.ebi.ac.uk/pdbsum/7lo7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lo7 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Membrane protein efflux pumps confer antibiotic resistance by extruding structurally distinct compounds and lowering their intracellular concentration. Yet, there are no clinically approved drugs to inhibit efflux pumps, which would potentiate the efficacy of existing antibiotics rendered ineffective by drug efflux. Here we identified synthetic antigen-binding fragments (Fabs) that inhibit the quinolone transporter NorA from methicillin-resistant Staphylococcus aureus (MRSA). Structures of two NorA-Fab complexes determined using cryo-electron microscopy reveal a Fab loop deeply inserted in the substrate-binding pocket of NorA. An arginine residue on this loop interacts with two neighboring aspartate and glutamate residues essential for NorA-mediated antibiotic resistance in MRSA. Peptide mimics of the Fab loop inhibit NorA with submicromolar potency and ablate MRSA growth in combination with the antibiotic norfloxacin. These findings establish a class of peptide inhibitors that block antibiotic efflux in MRSA by targeting indispensable residues in NorA without the need for membrane permeability.

Structural basis for inhibition of the drug efflux pump NorA from Staphylococcus aureus.,Brawley DN, Sauer DB, Li J, Zheng X, Koide A, Jedhe GS, Suwatthee T, Song J, Liu Z, Arora PS, Koide S, Torres VJ, Wang DN, Traaseth NJ Nat Chem Biol. 2022 Jul;18(7):706-712. doi: 10.1038/s41589-022-00994-9. Epub 2022 , Mar 31. PMID:35361990<ref>PMID:35361990</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7lo7" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Staphylococcus aureus]]
[[Category: Brawley DN]]
[[Category: Koide A]]
[[Category: Koide S]]
[[Category: Sauer DB]]
[[Category: Song JM]]
[[Category: Traaseth NJ]]
[[Category: Wang DN]]