6xvf

Crystal structure of bovine cytochrome bc1 in complex with tetrahydro-quinolone inhibitor JAG021Crystal structure of bovine cytochrome bc1 in complex with tetrahydro-quinolone inhibitor JAG021

Structural highlights 6xvf is a 10 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.5Å Ligands: , , , , , , , , , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CYB_BOVIN Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is a respiratory chain that generates an electrochemical potential coupled to ATP synthesis. Publication Abstract from PubMed Apicomplexan infections cause substantial morbidity and mortality, worldwide. New, improved therapies are needed. Herein, we create a next generation anti-apicomplexan lead compound, JAG21, a tetrahydroquinolone, with increased sp3-character to improve parasite selectivity. Relative to other cytochrome b inhibitors, JAG21 has improved solubility and ADMET properties, without need for pro-drug. JAG21 significantly reduces Toxoplasma gondii tachyzoites and encysted bradyzoites in vitro, and in primary and established chronic murine infections. Moreover, JAG21 treatment leads to 100% survival. Further, JAG21 is efficacious against drug-resistant Plasmodium falciparum in vitro. Causal prophylaxis and radical cure are achieved after P. berghei sporozoite infection with oral administration of a single dose (2.5 mg/kg) or 3 days treatment at reduced dose (0.625 mg/kg/day), eliminating parasitemia, and leading to 100% survival. Enzymatic, binding, and co-crystallography/pharmacophore studies demonstrate selectivity for apicomplexan relative to mammalian enzymes. JAG21 has significant promise as a pre-clinical candidate for prevention, treatment, and cure of toxoplasmosis and malaria. Potent Tetrahydroquinolone Eliminates Apicomplexan Parasites.,McPhillie MJ, Zhou Y, Hickman MR, Gordon JA, Weber CR, Li Q, Lee PJ, Amporndanai K, Johnson RM, Darby H, Woods S, Li ZH, Priestley RS, Ristroph KD, Biering SB, El Bissati K, Hwang S, Hakim FE, Dovgin SM, Lykins JD, Roberts L, Hargrave K, Cong H, Sinai AP, Muench SP, Dubey JP, Prud'homme RK, Lorenzi HA, Biagini GA, Moreno SN, Roberts CW, Antonyuk SV, Fishwick CWG, McLeod R Front Cell Infect Microbiol. 2020 Jun 9;10:203. doi: 10.3389/fcimb.2020.00203., eCollection 2020. PMID:32626661 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cytochrome C 3D structures Cytochrome bc1 3D structures

spinqualitylabelsall models 6xvf, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image