View source for 8ynz


==The structure of EfpA_BRD-8000.3 complex==
<StructureSection load='8ynz' size='340' side='right'caption='[[8ynz]], [[Resolution|resolution]] 3.41&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ynz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8YNZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8YNZ 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]] 3.41&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1AQR:(1~{S},3~{S})-~{N}-(6-bromanyl-5-pyrimidin-2-yl-pyridin-2-yl)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropane-1-carboxamide'>A1AQR</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=8ynz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ynz OCA], [https://pdbe.org/8ynz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ynz RCSB], [https://www.ebi.ac.uk/pdbsum/8ynz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ynz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/EFPA_MYCTU EFPA_MYCTU] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
EfpA, the first major facilitator superfamily (MFS) protein identified in Mycobacterium tuberculosis (Mtb), is an essential efflux pump implicated in resistance to multiple drugs. EfpA-inhibitors have been developed to kill drug-tolerant Mtb. However, the biological function of EfpA has not yet been elucidated. Here, we present the cryo-EM structures of EfpA complexed with lipids or the inhibitor BRD-8000.3 at resolutions of 2.9 A and 3.4 A, respectively. Unexpectedly, EfpA forms an antiparallel dimer. Functional studies reveal that EfpA is a lipid transporter and BRD-8000.3 inhibits its lipid transport activity. Intriguingly, the mutation V319F, known to confer resistance to BRD-8000.3, alters the expression level and oligomeric state of EfpA. Based on our results and the observation of other antiparallel dimers in the MFS family, we propose an antiparallel-function model of EfpA. Collectively, our work provides structural and functional insights into EfpA's role in lipid transport and drug resistance, which would accelerate the development of antibiotics against this promising drug target.

Structure and function of Mycobacterium tuberculosis EfpA as a lipid transporter and its inhibition by BRD-8000.3.,Li D, Zhang X, Yao Y, Sun X, Sun J, Ma X, Yuan K, Bai G, Pang X, Hua R, Guo T, Mi Y, Wu L, Zhang J, Wu Y, Liu Y, Wang P, Wong CCL, Chen XW, Xiao H, Gao GF, Gao F Proc Natl Acad Sci U S A. 2024 Oct 29;121(44):e2412653121. doi: , 10.1073/pnas.2412653121. Epub 2024 Oct 23. PMID:39441632<ref>PMID:39441632</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ynz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Li DL]]
[[Category: Sun JQ]]