View source for 6xvf


==Crystal structure of bovine cytochrome bc1 in complex with tetrahydro-quinolone inhibitor JAG021==
<StructureSection load='6xvf' size='340' side='right'caption='[[6xvf]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6xvf]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XVF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XVF FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6PE:1,2-DIHEXANOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>6PE</scene>, <scene name='pdbligand=CDL:CARDIOLIPIN'>CDL</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=JAG:2-methyl-3-[4-[4-(trifluoromethyloxy)phenoxy]phenyl]-5,6,7,8-tetrahydro-3~{H}-quinolin-4-one'>JAG</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=PEE:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>PEE</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=PX4:1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PX4</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=6xvf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xvf OCA], [https://pdbe.org/6xvf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xvf RCSB], [https://www.ebi.ac.uk/pdbsum/6xvf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xvf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/QCR1_BOVIN QCR1_BOVIN] This is a component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is part of the mitochondrial respiratory chain. This protein may mediate formation of the complex between cytochromes c and c1.
<div style="background-color:#fffaf0;">
== 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<ref>PMID:32626661</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6xvf" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cytochrome C 3D structures|Cytochrome C 3D structures]]
*[[Cytochrome bc1 3D structures|Cytochrome bc1 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Large Structures]]
[[Category: Amporndanai K]]
[[Category: Antonyuk SV]]
[[Category: Hasnain SS]]