7z3l
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7z3l]] 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=7Z3L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z3L FirstGlance]. <br> | <table><tr><td colspan='2'>[[7z3l]] 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=7Z3L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z3L FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7NB:2-[[2-ethyl-8-methyl-6-[4-[2-(3-oxidanylazetidin-1-yl)-2-oxidanylidene-ethyl]piperazin-1-yl]imidazo[1,2-a]pyridin-3-yl]-methyl-amino]-4-(4-fluorophenyl)-1,3-thiazole-5-carbonitrile'>7NB</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.4Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7NB:2-[[2-ethyl-8-methyl-6-[4-[2-(3-oxidanylazetidin-1-yl)-2-oxidanylidene-ethyl]piperazin-1-yl]imidazo[1,2-a]pyridin-3-yl]-methyl-amino]-4-(4-fluorophenyl)-1,3-thiazole-5-carbonitrile'>7NB</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</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=7z3l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z3l OCA], [https://pdbe.org/7z3l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z3l RCSB], [https://www.ebi.ac.uk/pdbsum/7z3l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z3l 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=7z3l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z3l OCA], [https://pdbe.org/7z3l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z3l RCSB], [https://www.ebi.ac.uk/pdbsum/7z3l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z3l ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/ENPP2_RAT ENPP2_RAT] | [https://www.uniprot.org/uniprot/ENPP2_RAT ENPP2_RAT] | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Autotaxin (ATX; ENPP2) produces the lipid mediator lysophosphatidic acid (LPA) that signals through disparate EDG (LPA(1-3)) and P2Y (LPA(4-6)) G protein-coupled receptors. ATX/LPA promotes several (patho)physiological processes, including in pulmonary fibrosis, thus serving as an attractive drug target. However, it remains unclear if clinical outcome depends on how different types of ATX inhibitors modulate the ATX/LPA signaling axis. Here, we show that the ATX "tunnel" is crucial for conferring key aspects of ATX/LPA signaling and dictates cellular responses independent of ATX catalytic activity, with a preference for activation of P2Y LPA receptors. The efficacy of the ATX/LPA signaling responses are abrogated more efficiently by tunnel-binding inhibitors, such as ziritaxestat (GLPG1690), compared with inhibitors that exclusively target the active site, as shown in primary lung fibroblasts and a murine model of radiation-induced pulmonary fibrosis. Our results uncover a receptor-selective signaling mechanism for ATX, implying clinical benefit for tunnel-targeting ATX inhibitors. | ||
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| - | Autotaxin facilitates selective LPA receptor signaling.,Salgado-Polo F, Borza R, Matsoukas MT, Marsais F, Jagerschmidt C, Waeckel L, Moolenaar WH, Ford P, Heckmann B, Perrakis A Cell Chem Biol. 2023 Jan 19;30(1):69-84.e14. doi: 10.1016/j.chembiol.2022.12.006. , Epub 2023 Jan 13. PMID:36640760<ref>PMID:36640760</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 7z3l" style="background-color:#fffaf0;"></div> | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 08:01, 7 February 2024
Autotaxin in complex with hybrid compound ziritaxestat (GLPG1690)
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