7rh5

Mycobacterial CIII2CIV2 supercomplex, Inhibitor free

spinqualitylabelsall models 7rh5, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7rh5 is a 20 chain structure with sequence from Mycolicibacterium smegmatis MC2 155. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3Å Ligands: 9XX, 9Y0, 9YF, CDL, CU, FES, HEA, HEC, HEM, MQ9, PLM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0R052_MYCS2 Publication Abstract from PubMed The imidazopyridine telacebec, also known as Q203, is one of only a few new classes of compounds in more than 50 years with demonstrated antituberculosis activity in humans. Telacebec inhibits the mycobacterial respiratory supercomplex composed of complexes III and IV (CIII(2)CIV(2)). In mycobacterial electron transport chains, CIII(2)CIV(2) replaces canonical CIII and CIV, transferring electrons from the intermediate carrier menaquinol to the final acceptor, molecular oxygen, while simultaneously transferring protons across the inner membrane to power ATP synthesis. We show that telacebec inhibits the menaquinol:oxygen oxidoreductase activity of purified Mycobacterium smegmatis CIII(2)CIV(2) at concentrations similar to those needed to inhibit electron transfer in mycobacterial membranes and Mycobacterium tuberculosis growth in culture. We then used electron cryomicroscopy (cryoEM) to determine structures of CIII(2)CIV(2) both in the presence and absence of telacebec. The structures suggest that telacebec prevents menaquinol oxidation by blocking two different menaquinol binding modes to prevent CIII(2)CIV(2) activity. Structure of mycobacterial CIII(2)CIV(2) respiratory supercomplex bound to the tuberculosis drug candidate telacebec (Q203).,Yanofsky DJ, Di Trani JM, Krol S, Abdelaziz R, Bueler SA, Imming P, Brzezinski P, Rubinstein JL Elife. 2021 Sep 30;10:e71959. doi: 10.7554/eLife.71959. PMID:34590581 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cytochrome bc1 3D structures

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