5m0s
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure-based evolution of a hybrid steroid series of Autotaxin inhibitors== | |
| + | <StructureSection load='5m0s' size='340' side='right'caption='[[5m0s]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5m0s]] 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=5M0S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5M0S 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]] 2.1Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7CW:[3,5-bis(chloranyl)phenyl]methyl+~{N}-[2-[[(4~{R})-4-[(3~{R},5~{S},7~{S},8~{R},9~{S},10~{S},13~{R},14~{S},17~{R})-10,13-dimethyl-3,7-bis(oxidanyl)-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1~{H}-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]ethyl]carbamate'>7CW</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=5m0s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m0s OCA], [https://pdbe.org/5m0s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5m0s RCSB], [https://www.ebi.ac.uk/pdbsum/5m0s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5m0s 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 produces the bioactive lipid lysophosphatidic acid (LPA) and is a drug target of considerable interest for numerous pathologies. We report the expedient, structure-guided evolution of weak physiological allosteric inhibitors (bile salts) into potent competitive Autotaxin inhibitors that do not interact with the catalytic site. Functional data confirms that our lead compound attenuates LPA mediated signaling in cells and reduces LPA synthesis in vivo, providing a promising natural product derived scaffold for drug discovery. | ||
| - | + | Rational Design of Autotaxin Inhibitors by Structural Evolution of Endogenous Modulators.,Keune WJ, Potjewyd F, Heidebrecht T, Salgado-Polo F, Macdonald SJ, Chelvarajan L, Abdel Latif A, Soman S, Morris AJ, Watson AJ, Jamieson C, Perrakis A J Med Chem. 2017 Mar 9;60(5):2006-2017. doi: 10.1021/acs.jmedchem.6b01743. Epub, 2017 Feb 16. PMID:28165241<ref>PMID:28165241</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5m0s" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures|Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Rattus norvegicus]] | ||
| + | [[Category: Heidebrecht T]] | ||
| + | [[Category: Keune W-J]] | ||
| + | [[Category: Perrakis A]] | ||
Current revision
Structure-based evolution of a hybrid steroid series of Autotaxin inhibitors
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