7bdc: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='7bdc' size='340' side='right'caption='[[7bdc]], [[Resolution|resolution]] 1.32Å' scene=''> | <StructureSection load='7bdc' size='340' side='right'caption='[[7bdc]], [[Resolution|resolution]] 1.32Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7bdc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BDC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BDC FirstGlance]. <br> | <table><tr><td colspan='2'>[[7bdc]] 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=7BDC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BDC 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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=WNA:1-methyl-N-[(2-methylphenyl)methyl]-1H-tetrazol-5-amine'>WNA</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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=WNA:1-methyl-N-[(2-methylphenyl)methyl]-1H-tetrazol-5-amine'>WNA</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=7bdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bdc OCA], [https://pdbe.org/7bdc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bdc RCSB], [https://www.ebi.ac.uk/pdbsum/7bdc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bdc 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=7bdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bdc OCA], [https://pdbe.org/7bdc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bdc RCSB], [https://www.ebi.ac.uk/pdbsum/7bdc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bdc 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 == | ||
| Line 24: | Line 22: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Jones | [[Category: Jones EY]] | ||
[[Category: Zhao | [[Category: Zhao Y]] | ||
Revision as of 07:37, 8 September 2022
Notum Fragment 923Notum Fragment 923
Structural highlights
Function[NOTUM_HUMAN] May deacetylate GlcNAc residues on cell surface glycans. Publication Abstract from PubMedThe 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 >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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||