6wtd

Monomer yeast ATP synthase Fo reconstituted in nanodisc with inhibitor of Bedaquiline bound

spinqualitylabelsall models 6wtd, resolution 4.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6wtd is a 16 chain structure with sequence from Saccharomyces cerevisiae and Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.2Å Ligands: FME Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also ATPase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA