3tgu: Difference between revisions

Latest revision as of 10:19, 13 August 2026

Cytochrome bc1 complex from chicken with pfvs-designed moa inhibitor bound

Structural highlights

3tgu is a 20 chain structure with sequence from Gallus gallus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.7Å
Ligands:	AME, BOG, CDL, FES, FME, GOL, HEC, HEM, PEE, UQ, WF3
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

D0VX31_CHICK

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hao GF, Wang F, Li H, Zhu XL, Yang WC, Huang LS, Wu JW, Berry EA, Yang GF. Computational Discovery of Picomolar Q(o) Site Inhibitors of Cytochrome bc(1) Complex. J Am Chem Soc. 2012 Jun 27. PMID:22690928 doi:10.1021/ja3001908

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OCA

[1] Hao GF, Wang F, Li H, Zhu XL, Yang WC, Huang LS, Wu JW, Berry EA, Yang GF. Computational Discovery of Picomolar Q(o) Site Inhibitors of Cytochrome bc(1) Complex. J Am Chem Soc. 2012 Jun 27. PMID:22690928 doi:10.1021/ja3001908

[1]

@@ Line 1: / Line 1: @@
 ==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=''>
+<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 [http://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 [http://oca.weizmann.ac.il/oca-docs/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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=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=UNL:UNKNOWN+LIGAND'>UNL</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>
+</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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=AME:N-ACETYLMETHIONINE'>AME</scene>, <scene name='pdbligand=FME:N-FORMYLMETHIONINE'>FME</scene>, <scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3l71|3l71]]</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquinol--cytochrome-c_reductase Ubiquinol--cytochrome-c reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.10.2.2 1.10.2.2] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3tgu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tgu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tgu RCSB], [http://www.ebi.ac.uk/pdbsum/3tgu PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/D0VX30_CHICK D0VX30_CHICK]] Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is part of the mitochondrial respiratory chain (By similarity).[PIRNR:PIRNR000022] [[http://www.uniprot.org/uniprot/CYB_CHICK CYB_CHICK]] 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 (By similarity). [[http://www.uniprot.org/uniprot/UCRI_CHICK UCRI_CHICK]] 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 (By similarity).
+[https://www.uniprot.org/uniprot/D0VX31_CHICK D0VX31_CHICK]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 18: @@
 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 complex|Cytochrome bc1 complex]]
+*[[Cytochrome bc1 3D structures|Cytochrome bc1 3D structures]]
 == References ==
 <references/>
@@ Line 27: / Line 27: @@
 </StructureSection>
 [[Category: Gallus gallus]]
-[[Category: Ubiquinol--cytochrome-c reductase]]
+[[Category: Large Structures]]
-[[Category: Berry, E A]]
+[[Category: Berry EA]]
-[[Category: Huang, L S]]
+[[Category: Huang L-S]]
-[[Category: Yang, G F]]
+[[Category: Yang G-F]]
-[[Category: Complex iii]]
-[[Category: Cytochrome b]]
-[[Category: Cytochrome bc1]]
-[[Category: Cytochrome c1]]
-[[Category: Electron transport]]
-[[Category: Heme]]
-[[Category: Heme protein]]
-[[Category: Inner membrane]]
-[[Category: Iron]]
-[[Category: Iron-sulfur]]
-[[Category: Membrane]]
-[[Category: Membrane protein]]
-[[Category: Metal-binding]]
-[[Category: Mitochondrial inner membrane]]
-[[Category: Mitochondrial processing protein]]
-[[Category: Mitochondrion]]
-[[Category: Oxidoreductase]]
-[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
-[[Category: Redox enzyme]]
-[[Category: Respiratory chain]]
-[[Category: Rieske iron sulfur protein]]
-[[Category: Strobilurins binding]]
-[[Category: Transit peptide]]
-[[Category: Transmembrane]]
-[[Category: Ubiquinone]]

3tgu: Difference between revisions

Latest revision as of 10:19, 13 August 2026

Cytochrome bc1 complex from chicken with pfvs-designed moa inhibitor bound

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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