View source for 6wtd


==Monomer yeast ATP synthase Fo reconstituted in nanodisc with inhibitor of Bedaquiline bound==
<StructureSection load='6wtd' size='340' side='right'caption='[[6wtd]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6wtd]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WTD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WTD 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]] 4.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FME:N-FORMYLMETHIONINE'>FME</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=6wtd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wtd OCA], [https://pdbe.org/6wtd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wtd RCSB], [https://www.ebi.ac.uk/pdbsum/6wtd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wtd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ATP9_YEAST ATP9_YEAST] Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain. A homomeric c-ring of probably 10 subunits is part of the complex rotary element.
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== Publication Abstract from PubMed ==
Bedaquiline (BDQ, Sirturo) has been approved to treat multidrug resistant forms of Mycobacterium tuberculosis. Prior studies suggested that BDQ was a selective inhibitor of the ATP synthase from M. tuberculosis. However, Sirturo treatment leads to an increased risk of cardiac arrhythmias and death, raising the concern that this adverse effect results from inhibition at a secondary site. Here we show that BDQ is a potent inhibitor of the yeast and human mitochondrial ATP synthases. Single-particle cryo-EM reveals that the site of BDQ inhibition partially overlaps with that of the inhibitor oligomycin. Molecular dynamics simulations indicate that the binding mode of BDQ to this site is similar to that previously seen for a mycobacterial enzyme, explaining the observed lack of selectivity. We propose that derivatives of BDQ ought to be made to increase its specificity toward the mycobacterial enzyme and thereby reduce the side effects for patients that are treated with Sirturo.

Bedaquiline inhibits the yeast and human mitochondrial ATP synthases.,Luo M, Zhou W, Patel H, Srivastava AP, Symersky J, Bonar MM, Faraldo-Gomez JD, Liao M, Mueller DM Commun Biol. 2020 Aug 19;3(1):452. doi: 10.1038/s42003-020-01173-z. PMID:32814813<ref>PMID:32814813</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 6wtd" style="background-color:#fffaf0;"></div>

==See Also==
*[[ATPase 3D structures|ATPase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae S288C]]
[[Category: Liao MF]]
[[Category: Luo M]]
[[Category: Mueller DM]]
[[Category: Srivastava AP]]
[[Category: Symersky J]]