8bt5: Difference between revisions

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 == Structural highlights ==
 <table><tr><td colspan='2'>[[8bt5]] 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=8BT5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BT5 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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=REH:1-(4-fluoranylspiro[2~{H}-indole-3,1-cyclobutane]-1-yl)ethanone'>REH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.4&#8491;</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=REH:1-(4-fluoranylspiro[2~{H}-indole-3,1-cyclobutane]-1-yl)ethanone'>REH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=8bt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bt5 OCA], [https://pdbe.org/8bt5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bt5 RCSB], [https://www.ebi.ac.uk/pdbsum/8bt5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bt5 ProSAT]</span></td></tr>
 </table>
 == Function ==
 [https://www.uniprot.org/uniprot/NOTUM_HUMAN NOTUM_HUMAN] May deacetylate GlcNAc residues on cell surface glycans.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+N-Acyl indolines 4 are potent, non-covalent Notum inhibitors developed from a covalent virtual screening hit 2a. The lead compounds were simple to synthesise, achieved excellent potency in a biochemical Notum-OPTS assay and restored Wnt signalling in a cell-based TCF/LEF reporter assay. Multiple high resolution X-ray structures established a common binding mode of these inhibitors with the indoline bound centred in the palmiteolate pocket with key interactions being aromatic stacking and a water mediated hydrogen bond to the oxyanion hole. These N-acyl indolines 4 will be useful tools for use in vitro studies to investigate the role of Notum in disease models, especially when paired with a structurally related covalent inhibitor (e.g. 4w and 2a). Overall, this study highlights the designed switch from covalent to non-covalent Notum inhibitors and so illustrates a complementary approach for hit generation and target inhibition.
+Designed switch from covalent to non-covalent inhibitors of carboxylesterase Notum activity.,Atkinson BN, Willis NJ, Zhao Y, Patel C, Frew S, Costelloe K, Magno L, Svensson F, Jones EY, Fish PV Eur J Med Chem. 2023 May 5;251:115132. doi: 10.1016/j.ejmech.2023.115132. Epub , 2023 Jan 21. PMID:36934521<ref>PMID:36934521</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 8bt5" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>