View source for 7jgc


==Cryo-EM structure of bedaquiline-saturated Mycobacterium smegmatis ATP synthase FO region==
<StructureSection load='7jgc' size='340' side='right'caption='[[7jgc]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7jgc]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis Mycolicibacterium smegmatis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JGC 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]] 3.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BQ1:BEDAQUILINE'>BQ1</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=7jgc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jgc OCA], [https://pdbe.org/7jgc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jgc RCSB], [https://www.ebi.ac.uk/pdbsum/7jgc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jgc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0R206_MYCS2 A0R206_MYCS2] Key component of the proton channel; it plays a direct role in the translocation of protons across the membrane.[HAMAP-Rule:MF_01393][RuleBase:RU000483]
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== Publication Abstract from PubMed ==
Tuberculosis-the world's leading cause of death by infectious disease-is increasingly resistant to current first-line antibiotics(1). The bacterium Mycobacterium tuberculosis (which causes tuberculosis) can survive low-energy conditions, allowing infections to remain dormant and decreasing their susceptibility to many antibiotics(2). Bedaquiline was developed in 2005 from a lead compound identified in a phenotypic screen against Mycobacterium smegmatis(3). This drug can sterilize even latent M. tuberculosisï»¿ infections(4) and has become a cornerstone of treatment for multidrug-resistant and extensively drug-resistant tuberculosis(1,5,6). Bedaquiline targets the mycobacterial ATP synthase(3), which is an essential enzyme in the obligate aerobic Mycobacterium genus(3,7), but how it binds the intact enzyme is unknown. Here we determined cryo-electron microscopy structures of M. smegmatis ATP synthase alone and in complex with bedaquiline. The drug-free structure suggests that hook-like extensions from the alpha-subunits prevent the enzyme from running in reverse, inhibiting ATP hydrolysis and preserving energy in hypoxic conditions. Bedaquiline binding induces large conformational changes in the ATP synthase, creating tight binding pockets at the interface of subunits a and c that explain the potency of this drug as an antibiotic for tuberculosis.

Structure of mycobacterial ATP synthase bound to the tuberculosis drug bedaquiline.,Guo H, Courbon GM, Bueler SA, Mai J, Liu J, Rubinstein JL Nature. 2021 Jan;589(7840):143-147. doi: 10.1038/s41586-020-3004-3. Epub 2020 Dec , 9. PMID:33299175<ref>PMID:33299175</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7jgc" style="background-color:#fffaf0;"></div>

==See Also==
*[[ATPase 3D structures|ATPase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycolicibacterium smegmatis]]
[[Category: Courbon GM]]
[[Category: Guo H]]
[[Category: Rubinstein JL]]