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==Crystal Structure of Autotaxin and Compound 1== | ==Crystal Structure of Autotaxin and Compound 1== | ||
<StructureSection load='5l0b' size='340' side='right' caption='[[5l0b]], [[Resolution|resolution]] 2.41Å' scene=''> | <StructureSection load='5l0b' size='340' side='right'caption='[[5l0b]], [[Resolution|resolution]] 2.41Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5l0b]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L0B OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[5l0b]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L0B OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5L0B FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6ZM:1-{2-[(2,3-DIHYDRO-1H-INDEN-2-YL)AMINO]-7,8-DIHYDROPYRIDO[4,3-D]PYRIMIDIN-6(5H)-YL}ETHAN-1-ONE'>6ZM</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand= | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6ZM:1-{2-[(2,3-DIHYDRO-1H-INDEN-2-YL)AMINO]-7,8-DIHYDROPYRIDO[4,3-D]PYRIMIDIN-6(5H)-YL}ETHAN-1-ONE'>6ZM</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5l0e|5l0e]], [[5l0k|5l0k]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5l0e|5l0e]], [[5l0k|5l0k]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Enpp2, Atx, Npps2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Alkylglycerophosphoethanolamine_phosphodiesterase Alkylglycerophosphoethanolamine phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.39 3.1.4.39] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Alkylglycerophosphoethanolamine_phosphodiesterase Alkylglycerophosphoethanolamine phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.39 3.1.4.39] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5l0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l0b OCA], [http://pdbe.org/5l0b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l0b RCSB], [http://www.ebi.ac.uk/pdbsum/5l0b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l0b ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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</div> | </div> | ||
<div class="pdbe-citations 5l0b" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5l0b" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures|Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Alkylglycerophosphoethanolamine phosphodiesterase]] | [[Category: Alkylglycerophosphoethanolamine phosphodiesterase]] | ||
[[Category: Buffalo rat]] | |||
[[Category: Large Structures]] | |||
[[Category: Durbin, J D]] | [[Category: Durbin, J D]] | ||
[[Category: Hydrolase-hydrolase inhibitor complex]] | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
[[Category: Phospholipase]] | [[Category: Phospholipase]] | ||
Revision as of 09:38, 5 August 2020
Crystal Structure of Autotaxin and Compound 1Crystal Structure of Autotaxin and Compound 1
Structural highlights
Publication Abstract from PubMedIn an effort to develop a novel therapeutic agent aimed at addressing the unmet need of patients with osteoarthritis pain, we set out to develop an inhibitor for autotaxin with excellent potency and physical properties to allow for the clinical investigation of autotaxin-induced nociceptive and neuropathic pain. An initial hit identification campaign led to an aminopyrimidine series with an autotaxin IC50 of 500 nM. X-ray crystallography enabled the optimization to a lead compound that demonstrated favorable potency (IC50 = 2 nM), PK properties, and a robust PK/PD relationship. Novel Autotaxin Inhibitors for the Treatment of Osteoarthritis Pain: Lead Optimization via Structure-Based Drug Design.,Jones SB, Pfeifer LA, Bleisch TJ, Beauchamp TJ, Durbin JD, Klimkowski VJ, Hughes NE, Rito CJ, Dao Y, Gruber JM, Bui H, Chambers MG, Chandrasekhar S, Lin C, McCann DJ, Mudra DR, Oskins JL, Swearingen CA, Thirunavukkarasu K, Norman BH ACS Med Chem Lett. 2016 Aug 2;7(9):857-61. doi: 10.1021/acsmedchemlett.6b00207., eCollection 2016 Sep 8. PMID:27660691[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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