5lia
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of murine autotaxin in complex with a small molecule inhibitor== | |
| + | <StructureSection load='5lia' size='340' side='right' caption='[[5lia]], [[Resolution|resolution]] 1.92Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5lia]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LIA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LIA FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6XN:~{N}-[(1~{S})-1-(4-CHLOROPHENYL)ETHYL]-3-[3-[[4-(TRIFLUOROMETHYLOXY)PHENYL]METHYL]IMIDAZO[4,5-B]PYRIDIN-2-YL]PROPANAMIDE'>6XN</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5lia FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lia OCA], [http://pdbe.org/5lia PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lia RCSB], [http://www.ebi.ac.uk/pdbsum/5lia PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lia ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/ENPP2_MOUSE ENPP2_MOUSE]] Note=May contribute to obesity. | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/ENPP2_MOUSE ENPP2_MOUSE]] Hydrolyzes lysophospholipids to produce lysophosphatidic acid (LPA) in extracellular fluids. Major substrate is lysophosphatidylcholine. Also can act on sphingosylphosphphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility. Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP. Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation. Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein. May have a role in induction of parturition. Possible involvement in cell proliferation and adipose tissue development. Tumor cell motility-stimulating factor.<ref>PMID:15700135</ref> <ref>PMID:17208043</ref> <ref>PMID:21240269</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The autotoxin-lysophosphatidic acid (ATX-LPA) axis has been implicated in several disease conditions including inflammation, fibrosis and cancer. This makes ATX an attractive drug target and its inhibition may lead to useful therapeutic agents. Through a high throughput screen (HTS) we identified a series of small molecule inhibitors of ATX which have subsequently been optimized for potency, selectivity and developability properties. This has delivered drug-like compounds such as 9v (CRT0273750) which modulate LPA levels in plasma and are suitable for in vivo studies. X-ray crystallography has revealed that these compounds have an unexpected binding mode in that they do not interact with the active site zinc ions but instead occupy the hydrophobic LPC pocket extending from the active of ATX together with the occupying the LPA 'exit' channel. | ||
| - | + | Discovery of potent inhibitors of the lysophospholipase autotaxin.,Shah P, Cheasty A, Foxton C, Raynham T, Farooq M, Gutierrez IF, Lejeune A, Pritchard M, Turnbull A, Pang L, Owen P, Boyd S, Stowell A, Jordan A, Hamilton NM, Hitchin JR, Stockley M, MacDonald E, Quesada MJ, Trivier E, Skeete J, Ovaa H, Moolenaar WH, Ryder H Bioorg Med Chem Lett. 2016 Oct 14. pii: S0960-894X(16)31064-2. doi:, 10.1016/j.bmcl.2016.10.036. PMID:27780639<ref>PMID:27780639</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | [[Category: | + | <div class="pdbe-citations 5lia" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Alkylglycerophosphoethanolamine phosphodiesterase]] | ||
| + | [[Category: Cheasty, A]] | ||
[[Category: Owen, P]] | [[Category: Owen, P]] | ||
[[Category: Pang, L]] | [[Category: Pang, L]] | ||
| - | [[Category: | + | [[Category: Raynham, T]] |
| - | [[Category: Turnbull, A | + | [[Category: Shah, P]] |
| + | [[Category: Turnbull, A P]] | ||
| + | [[Category: Autotaxin]] | ||
| + | [[Category: Enpp2]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Lysophospholipase d]] | ||
Revision as of 19:56, 9 December 2016
Crystal structure of murine autotaxin in complex with a small molecule inhibitor
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