7b84

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7b84]] 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=7B84 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B84 FirstGlance]. <br>
<table><tr><td colspan='2'>[[7b84]] 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=7B84 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B84 FirstGlance]. <br>
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</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=JFS:[4-(1H-benzimidazol-1-yl)phenyl]methanol'>JFS</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.36&#8491;</td></tr>
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<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=JFS:[4-(1H-benzimidazol-1-yl)phenyl]methanol'>JFS</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7b84 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b84 OCA], [https://pdbe.org/7b84 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b84 RCSB], [https://www.ebi.ac.uk/pdbsum/7b84 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b84 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=7b84 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b84 OCA], [https://pdbe.org/7b84 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b84 RCSB], [https://www.ebi.ac.uk/pdbsum/7b84 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b84 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/NOTUM_HUMAN NOTUM_HUMAN]] May deacetylate GlcNAc residues on cell surface glycans.
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[https://www.uniprot.org/uniprot/NOTUM_HUMAN NOTUM_HUMAN] May deacetylate GlcNAc residues on cell surface glycans.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The Wnt signaling suppressor Notum is a promising target for osteoporosis, Alzheimer's disease, and colorectal cancers. To develop novel Notum inhibitors, we used an X-ray crystallographic fragment screen with the Diamond-SGC Poised Library (DSPL) and identified 59 fragment hits from the analysis of 768 data sets. Fifty-eight of the hits were found bound at the enzyme catalytic pocket with potencies ranging from 0.5 to &gt;1000 muM. Analysis of the fragments' diverse binding modes, enzymatic inhibitory activities, and chemical properties led to the selection of six hits for optimization, and five of these resulted in improved Notum inhibitory potencies. One hit, 1-phenyl-1,2,3-triazole 7, and its related cluster members, have shown promising lead-like properties. These became the focus of our fragment development activities, resulting in compound 7d with IC50 0.0067 muM. The large number of Notum fragment structures and their initial optimization provided an important basis for further Notum inhibitor development.
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Structural Analysis and Development of Notum Fragment Screening Hits.,Zhao Y, Mahy W, Willis NJ, Woodward HL, Steadman D, Bayle ED, Atkinson BN, Sipthorp J, Vecchia L, Ruza RR, Harlos K, Jeganathan F, Constantinou S, Costa A, Kjaer S, Bictash M, Salinas PC, Whiting P, Vincent JP, Fish PV, Jones EY ACS Chem Neurosci. 2022 Jul 6;13(13):2060-2077. doi:, 10.1021/acschemneuro.2c00325. Epub 2022 Jun 22. PMID:35731924<ref>PMID:35731924</ref>
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==See Also==
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*[[Carboxylesterase 3D structures|Carboxylesterase 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7b84" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>

Revision as of 07:47, 1 May 2024

Notum-Fragment065

PDB ID 7b84

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