4bi0: Difference between revisions
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==Scaffold Focused Virtual Screening: Prospective Application to the Discovery of TTK Inhibitor== | ==Scaffold Focused Virtual Screening: Prospective Application to the Discovery of TTK Inhibitor== | ||
<StructureSection load='4bi0' size='340' side='right' caption='[[4bi0]], [[Resolution|resolution]] 2.84Å' scene=''> | <StructureSection load='4bi0' size='340' side='right'caption='[[4bi0]], [[Resolution|resolution]] 2.84Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4bi0]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4bi0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BI0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BI0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7PE:2-(2-(2-(2-(2-(2-ETHOXYETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHANOL'>7PE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=Z0W:5H-PYRIMIDO[5,4-B]INDOLE'>Z0W</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.84Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7PE:2-(2-(2-(2-(2-(2-ETHOXYETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHANOL'>7PE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=Z0W:5H-PYRIMIDO[5,4-B]INDOLE'>Z0W</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=4bi0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bi0 OCA], [https://pdbe.org/4bi0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bi0 RCSB], [https://www.ebi.ac.uk/pdbsum/4bi0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bi0 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/TTK_HUMAN TTK_HUMAN] Phosphorylates proteins on serine, threonine, and tyrosine. Probably associated with cell proliferation. Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphorylation) at the centromere, and for the mitotic checkpoint.<ref>PMID:18243099</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 18: | Line 18: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4bi0" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Dual specificity protein kinase|Dual specificity protein kinase]] | *[[Dual specificity protein kinase 3D structures|Dual specificity protein kinase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Blagg J]] | ||
[[Category: | [[Category: Brown N]] | ||
[[Category: | [[Category: Langdon SR]] | ||
[[Category: Westwood | [[Category: Westwood IM]] | ||
[[Category: | [[Category: Van Montfort RLM]] | ||
Latest revision as of 14:51, 20 December 2023
Scaffold Focused Virtual Screening: Prospective Application to the Discovery of TTK InhibitorScaffold Focused Virtual Screening: Prospective Application to the Discovery of TTK Inhibitor
Structural highlights
FunctionTTK_HUMAN Phosphorylates proteins on serine, threonine, and tyrosine. Probably associated with cell proliferation. Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphorylation) at the centromere, and for the mitotic checkpoint.[1] Publication Abstract from PubMedWe describe and apply a scaffold-focused virtual screen based upon scaffold trees to the mitotic kinase TTK (MPS1). Using level 1 of the scaffold tree, we perform both 2D and 3D similarity searches between a query scaffold and a level 1 scaffold library derived from a 2 million compound library; 98 compounds from 27 unique top-ranked level 1 scaffolds are selected for biochemical screening. We show that this scaffold-focused virtual screen prospectively identifies eight confirmed active compounds that are structurally differentiated from the query compound. In comparison, 100 compounds were selected for biochemical screening using a virtual screen based upon whole molecule similarity resulting in 12 confirmed active compounds that are structurally similar to the query compound. We elucidated the binding mode for four of the eight confirmed scaffold hops to TTK by determining their protein-ligand crystal structures; each represents a ligand-efficient scaffold for inhibitor design. Scaffold-Focused Virtual Screening: Prospective Application to the Discovery of TTK Inhibitors.,Langdon SR, Westwood IM, van Montfort RL, Brown N, Blagg J J Chem Inf Model. 2013 May 24;53(5):1100-12. doi: 10.1021/ci400100c. Epub 2013, May 14. PMID:23672464[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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