View source for 3tgu


==Cytochrome bc1 complex from chicken with pfvs-designed moa inhibitor bound==
<StructureSection load='3tgu' size='340' side='right'caption='[[3tgu]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3tgu]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TGU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TGU 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]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AME:N-ACETYLMETHIONINE'>AME</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=CDL:CARDIOLIPIN'>CDL</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=FME:N-FORMYLMETHIONINE'>FME</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PEE:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>PEE</scene>, <scene name='pdbligand=UQ:COENZYME+Q10,+(2Z,6E,10Z,14E,18E,22E,26Z)-ISOMER'>UQ</scene>, <scene name='pdbligand=WF3:METHYL+(2E)-3-METHOXY-2-[2-({[6-METHYL-3-(TRIFLUOROMETHYL)QUINOXALIN-2-YL]OXY}METHYL)PHENYL]PROP-2-ENOATE'>WF3</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=3tgu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tgu OCA], [https://pdbe.org/3tgu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tgu RCSB], [https://www.ebi.ac.uk/pdbsum/3tgu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tgu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/D0VX31_CHICK D0VX31_CHICK] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A critical challenge to the fragment-based drug discovery (FBDD) is its low-throughput nature due to the necessity of biophysical method-based fragment screening. Herein, a method of pharmacophore-linked fragment virtual screening (PFVS) was successfully developed. Its application yielded the first picomolar-range Q(o) site inhibitors of the cytochrome bc(1) complex, an important membrane protein for drug and fungicide discovery. Compared with the original hit compound 4 (K(i) = 881.80 nM, porcine bc(1)), the most potent compound 4f displayed 20 507-fold improved binding affinity (K(i) = 43.00 pM). Compound 4f was proved to be a noncompetitive inhibitor with respect to the substrate cytochrome c, but a competitive inhibitor with respect to the substrate ubiquinol. Additionally, we determined the crystal structure of compound 4e (K(i) = 83.00 pM) bound to the chicken bc(1) at 2.70 A resolution, providing a molecular basis for understanding its ultrapotency. To our knowledge, this study is the first application of the FBDD method in the discovery of picomolar inhibitors of a membrane protein. This work demonstrates that the novel PFVS approach is a high-throughput drug discovery method, independent of biophysical screening techniques.

Computational Discovery of Picomolar Q(o) Site Inhibitors of Cytochrome bc(1) Complex.,Hao GF, Wang F, Li H, Zhu XL, Yang WC, Huang LS, Wu JW, Berry EA, Yang GF J Am Chem Soc. 2012 Jun 27. PMID:22690928<ref>PMID:22690928</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3tgu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cytochrome bc1 3D structures|Cytochrome bc1 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Gallus gallus]]
[[Category: Large Structures]]
[[Category: Berry EA]]
[[Category: Huang L-S]]
[[Category: Yang G-F]]