8c4w
From Proteopedia
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(New page: '''Unreleased structure''' The entry 8c4w is ON HOLD Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of rat autotaxin and compound MEY-002== | |
| + | <StructureSection load='8c4w' size='340' side='right'caption='[[8c4w]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8c4w]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8C4W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8C4W FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5JK:7ALPHA-HYDROXYCHOLESTEROL'>5JK</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene>, <scene name='pdbligand=TIJ:5,7-bis(oxidanyl)-2-[1-(phenylmethyl)indol-3-yl]chromen-4-one'>TIJ</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8c4w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8c4w OCA], [https://pdbe.org/8c4w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8c4w RCSB], [https://www.ebi.ac.uk/pdbsum/8c4w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8c4w ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ENPP2_RAT ENPP2_RAT] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Autotaxin (ATX) is an enzyme primarily known for the production of lysophosphatidic acid. Being involved in the development of major human diseases, such as cancer and neurodegenerative diseases, the enzyme has been featured in multiple studies as a pharmacological target. We previously found that the cannabinoid tetrahydrocannabinol (THC) could bind and act as an excellent inhibitor of ATX. This study aims to use the cannabinoid scaffold as a starting point to find cannabinoid-unrelated ATX inhibitors, following a funnel down approach in which large chemical libraries sharing chemical similarities with THC were screened to identify lead scaffold types for optimization. This approach allowed us to identify compounds bearing chromone and indole scaffolds as promising ATX inhibitors. Further optimization led to MEY-003, which is characterized by the direct linkage of an N-pentyl indole to the 5,7-dihydroxychromone moiety. This molecule has potent inhibitory activity towards ATX-beta and ATX-É£ as evidenced by enzymatic studies and its mode of action was rationalized by structural biology studies using macromolecular X-ray crystallography. | ||
| - | + | Discovery of potent chromone-based autotaxin inhibitors inspired by cannabinoids.,Eymery MC, Nguyen KA, Basu S, Hausmann J, Tran-Nguyen VK, Seidel HP, Gutierrez L, Boumendjel A, McCarthy AA Eur J Med Chem. 2024 Jan 5;263:115944. doi: 10.1016/j.ejmech.2023.115944. Epub , 2023 Nov 10. PMID:37976710<ref>PMID:37976710</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8c4w" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Rattus norvegicus]] | ||
| + | [[Category: Eymery MC]] | ||
| + | [[Category: McCarthy AA]] | ||
Current revision
Crystal structure of rat autotaxin and compound MEY-002
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