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7nvh
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 7nvh is ON HOLD Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Cryo-EM structure of the mycolic acid transporter MmpL3 from M. tuberculosis== | |
| + | <StructureSection load='7nvh' size='340' side='right'caption='[[7nvh]], [[Resolution|resolution]] 3.02Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7nvh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NVH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NVH FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AV0:2-decyl-2-{[(4-O-alpha-D-glucopyranosyl-beta-D-glucopyranosyl)oxy]methyl}dodecyl+4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside'>AV0</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=7nvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nvh OCA], [https://pdbe.org/7nvh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nvh RCSB], [https://www.ebi.ac.uk/pdbsum/7nvh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nvh ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MMPL3_MYCTU MMPL3_MYCTU] Transports trehalose monomycolate (TMM) to the cell wall. Flips TMM across the inner membrane (PubMed:22252828, PubMed:22344175). Membrane potential is not required for this function. Transports probably phosphatidylethanolamine (PE) as well. Binds specifically both TMM and PE, but not trehalose dimycolate (TDM). Binds also diacylglycerol (DAG) and other phospholipids, including phosphatidylglycerol (PG), phosphatidylinositol (PI), and cardiolipin (CDL). Contributes to membrane potential, cell wall composition, antibiotic susceptibility and fitness (By similarity). Could also be part of a heme-iron acquisition system (PubMed:21383189).[UniProtKB:A0QP27]<ref>PMID:22252828</ref> <ref>PMID:22344175</ref> <ref>PMID:21383189</ref> Is the target of the antitubercular drug SQ109.<ref>PMID:22252828</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Tuberculosis (TB) is the leading cause of death from a single infectious agent and in 2019 an estimated 10 million people worldwide contracted the disease. Although treatments for TB exist, continual emergence of drug-resistant variants necessitates urgent development of novel antituberculars. An important new target is the lipid transporter MmpL3, which is required for construction of the unique cell envelope that shields Mycobacterium tuberculosis (Mtb) from the immune system. However, a structural understanding of the mutations in Mtb MmpL3 that confer resistance to the many preclinical leads is lacking, hampering efforts to circumvent resistance mechanisms. Here, we present the cryoelectron microscopy structure of Mtb MmpL3 and use it to comprehensively analyze the mutational landscape of drug resistance. Our data provide a rational explanation for resistance variants local to the central drug binding site, and also highlight a potential alternative route to resistance operating within the periplasmic domain. | ||
| - | + | Cryo-EM structure and resistance landscape of M. tuberculosis MmpL3: An emergent therapeutic target.,Adams O, Deme JC, Parker JL, Fowler PW, Lea SM, Newstead S Structure. 2021 Jun 28. pii: S0969-2126(21)00217-3. doi:, 10.1016/j.str.2021.06.013. PMID:34242558<ref>PMID:34242558</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7nvh" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mycobacterium tuberculosis]] | ||
| + | [[Category: Adams O]] | ||
| + | [[Category: Deme JC]] | ||
| + | [[Category: Lea SM]] | ||
| + | [[Category: Newstead S]] | ||
| + | [[Category: Parker JL]] | ||
Current revision
Cryo-EM structure of the mycolic acid transporter MmpL3 from M. tuberculosis
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