9s2u
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==1:1 complex of M.tuberculosis MmpL5 and M.smegmatis AcpM== | |
| + | <StructureSection load='9s2u' size='340' side='right'caption='[[9s2u]], [[Resolution|resolution]] 3.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9s2u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aequorea_victoria Aequorea victoria], [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] and [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9S2U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9S2U 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]] 3.2Å</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=9s2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9s2u OCA], [https://pdbe.org/9s2u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9s2u RCSB], [https://www.ebi.ac.uk/pdbsum/9s2u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9s2u ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MMPL5_MYCTU MMPL5_MYCTU] Part of an export system, which is required for biosynthesis and secretion of siderophores.<ref>PMID:23431276</ref> Overexpression of the system confers non-target based resistance to azoles, clofazimine and bedaquiline, via an efflux mechanism.<ref>PMID:18851927</ref> <ref>PMID:24590481</ref> <ref>PMID:25010492</ref> [https://www.uniprot.org/uniprot/GFP_AEQVI GFP_AEQVI] Energy-transfer acceptor. Its role is to transduce the blue chemiluminescence of the protein aequorin into green fluorescent light by energy transfer. Fluoresces in vivo upon receiving energy from the Ca(2+)-activated photoprotein aequorin. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Bedaquiline, an antitubercular drug that targets ATP-synthase, is a key component of a new oral drug regimen that has revolutionized the treatment of multidrug-resistant tuberculosis. Clinical bedaquiline resistance in Mycobacterium tuberculosis has rapidly emerged, primarily due to mutations in the transcriptional repressor Rv0678 that result in upregulation of the resistance-nodulation-division (RND) efflux pump MmpS5/MmpL5 (MmpS5L5). Here, to understand how MmpS5L5 effluxes bedaquiline, we determined the structure of the MmpS5L5 complex using cryo-electron microscopy, revealing a trimeric architecture distinct from the canonical tripartite RND efflux pumps of gram-negative bacteria. Structure prediction modeling in conjunction with functional genetic analysis indicates that it uses a periplasmic coiled-coil tube to transport molecules across the cell wall. Structure-guided genetic approaches identify MmpL5 mutations that alter bedaquiline transport; these mutations converge on a region in MmpL5 located in the lower portion of the periplasmic cavity, proximal to the outer leaflet of the inner membrane, suggesting a route for bedaquiline entry into the pump. While currently known clinical resistance to bedaquiline is due to pump upregulation, our findings that several MmpL5 variants increase bedaquiline efflux may presage the emergence of additional modes of clinical resistance. | ||
| - | + | Structural and functional analysis of the Mycobacterium tuberculosis MmpS5L5 efflux pump presages increased bedaquiline resistance.,Fountain AJ, Bohning J, McLaughlin SH, Morgan TE, Edelstein PH, Troll M, Lamers MH, Bharat TAM, Luisi BF, Ramakrishnan L Proc Natl Acad Sci U S A. 2025 Sep 30;122(39):e2516660122. doi: , 10.1073/pnas.2516660122. Epub 2025 Sep 23. PMID:40986343<ref>PMID:40986343</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 9s2u" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: Fountain | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Aequorea victoria]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mycobacterium tuberculosis]] | ||
| + | [[Category: Mycolicibacterium smegmatis MC2 155]] | ||
| + | [[Category: Fountain AJ]] | ||
| + | [[Category: Luisi BF]] | ||
| + | [[Category: Ramakrishan L]] | ||
Current revision
1:1 complex of M.tuberculosis MmpL5 and M.smegmatis AcpM
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