3tgu: Difference between revisions
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<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> | <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]] 2.7Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</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 | <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> | <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> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/D0VX31_CHICK D0VX31_CHICK] | [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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3tgu" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Cytochrome bc1 3D structures|Cytochrome bc1 3D structures]] | *[[Cytochrome bc1 3D structures|Cytochrome bc1 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Latest revision as of 10:19, 13 August 2026
Cytochrome bc1 complex from chicken with pfvs-designed moa inhibitor bound
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