7b50: Difference between revisions
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<StructureSection load='7b50' size='340' side='right'caption='[[7b50]], [[Resolution|resolution]] 1.33Å' scene=''> | <StructureSection load='7b50' size='340' side='right'caption='[[7b50]], [[Resolution|resolution]] 1.33Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7b50]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B50 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7b50]] 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=7B50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B50 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SXQ:3-(3,4-dichlorophenyl)sulfanyl-1$l^{4},2,7,8-tetrazabicyclo[4.3.0]nona-1(6),2,4,7-tetraen-9-one'>SXQ</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SXQ:3-(3,4-dichlorophenyl)sulfanyl-1$l^{4},2,7,8-tetrazabicyclo[4.3.0]nona-1(6),2,4,7-tetraen-9-one'>SXQ</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=7b50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b50 OCA], [https://pdbe.org/7b50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b50 RCSB], [https://www.ebi.ac.uk/pdbsum/7b50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b50 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=7b50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b50 OCA], [https://pdbe.org/7b50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b50 RCSB], [https://www.ebi.ac.uk/pdbsum/7b50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b50 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[https://www.uniprot.org/uniprot/NOTUM_HUMAN NOTUM_HUMAN]] May deacetylate GlcNAc residues on cell surface glycans. | [[https://www.uniprot.org/uniprot/NOTUM_HUMAN NOTUM_HUMAN]] May deacetylate GlcNAc residues on cell surface glycans. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Fish | [[Category: Fish P]] | ||
[[Category: Jones | [[Category: Jones EY]] | ||
Revision as of 07:35, 8 September 2022
Notum complex with ARUK3003778Notum complex with ARUK3003778
Structural highlights
Function[NOTUM_HUMAN] May deacetylate GlcNAc residues on cell surface glycans. Publication Abstract from PubMedNotum is a negative regulator of Wnt signaling acting through the hydrolysis of a palmitoleoylate ester, which is required for Wnt activity. Inhibitors of Notum could be of use in diseases where dysfunctional Notum activity is an underlying cause. A docking-based virtual screen (VS) of a large commercial library was used to shortlist 952 compounds for experimental validation as inhibitors of Notum. The VS was successful with 31 compounds having an IC50 < 500 nM. A critical selection process was then applied with two clusters and two singletons (1-4d) selected for hit validation. Optimization of 4d guided by structural biology identified potent inhibitors of Notum activity that restored Wnt/beta-catenin signaling in cell-based models. The [1,2,4]triazolo[4,3-b]pyradizin-3(2H)-one series 4 represent a new chemical class of Notum inhibitors and the first to be discovered by a VS campaign. These results demonstrate the value of VS with well-designed docking models based on X-ray structures. Virtual Screening Directly Identifies New Fragment-Sized Inhibitors of Carboxylesterase Notum with Nanomolar Activity.,Steadman D, Atkinson BN, Zhao Y, Willis NJ, Frew S, Monaghan A, Patel C, Armstrong E, Costelloe K, Magno L, Bictash M, Jones EY, Fish PV, Svensson F J Med Chem. 2022 Jan 13;65(1):562-578. doi: 10.1021/acs.jmedchem.1c01735. Epub, 2021 Dec 23. PMID:34939789[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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