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==Crystal structure of Autotaxin (ENPP2) with 7-alpha-hydroxycholesterol== | ==Crystal structure of Autotaxin (ENPP2) with 7-alpha-hydroxycholesterol== | ||
<StructureSection load='5dlt' size='340' side='right' caption='[[5dlt]], [[Resolution|resolution]] 1.60Å' scene=''> | <StructureSection load='5dlt' size='340' side='right'caption='[[5dlt]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5dlt]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DLT OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[5dlt]] is a 1 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=5DLT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5DLT FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5JK:7ALPHA-HYDROXYCHOLESTEROL'>5JK</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=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='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=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=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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></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=5dlt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dlt OCA], [http://pdbe.org/5dlt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dlt RCSB], [http://www.ebi.ac.uk/pdbsum/5dlt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dlt 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 5dlt" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5dlt" 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: Hausmann, J]] | [[Category: Hausmann, J]] | ||
[[Category: Joosten, R P]] | [[Category: Joosten, R P]] | ||
Revision as of 11:09, 8 April 2020
Crystal structure of Autotaxin (ENPP2) with 7-alpha-hydroxycholesterolCrystal structure of Autotaxin (ENPP2) with 7-alpha-hydroxycholesterol
Structural highlights
Publication Abstract from PubMedAutotaxin (ATX) generates the lipid mediator lysophosphatidic acid (LPA). ATX-LPA signalling is involved in multiple biological and pathophysiological processes, including vasculogenesis, fibrosis, cholestatic pruritus and tumour progression. ATX has a tripartite active site, combining a hydrophilic groove, a hydrophobic lipid-binding pocket and a tunnel of unclear function. We present crystal structures of rat ATX bound to 7alpha-hydroxycholesterol and the bile salt tauroursodeoxycholate (TUDCA), showing how the tunnel selectively binds steroids. A structure of ATX simultaneously harbouring TUDCA in the tunnel and LPA in the pocket, together with kinetic analysis, reveals that bile salts act as partial non-competitive inhibitors of ATX, thereby attenuating LPA receptor activation. This unexpected interplay between ATX-LPA signalling and select steroids, notably natural bile salts, provides a molecular basis for the emerging association of ATX with disorders associated with increased circulating levels of bile salts. Furthermore, our findings suggest potential clinical implications in the use of steroid drugs. Steroid binding to Autotaxin links bile salts and lysophosphatidic acid signalling.,Keune WJ, Hausmann J, Bolier R, Tolenaars D, Kremer A, Heidebrecht T, Joosten RP, Sunkara M, Morris AJ, Matas-Rico E, Moolenaar WH, Oude Elferink RP, Perrakis A Nat Commun. 2016 Apr 14;7:11248. doi: 10.1038/ncomms11248. PMID:27075612[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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