5m0e: Difference between revisions
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New page: '''Unreleased structure''' The entry 5m0e is ON HOLD Authors: Description: Category: Unreleased Structures |
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==Structure-based evolution of a hybrid steroid series of Autotaxin inhibitors== | |||
<StructureSection load='5m0e' size='340' side='right'caption='[[5m0e]], [[Resolution|resolution]] 1.95Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5m0e]] 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=5M0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5M0E 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]] 1.95Å</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=7CR:[3,5-bis(chloranyl)phenyl]methyl+4-[(3~{R})-3-oxidanyl-3-(2-oxidanylidene-3~{H}-1,3-benzoxazol-6-yl)propyl]piperazine-1-carboxylate'>7CR</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5m0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m0e OCA], [https://pdbe.org/5m0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5m0e RCSB], [https://www.ebi.ac.uk/pdbsum/5m0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5m0e 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 5m0e" 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]] | |||
Latest revision as of 21:19, 1 November 2023
Structure-based evolution of a hybrid steroid series of Autotaxin inhibitorsStructure-based evolution of a hybrid steroid series of Autotaxin inhibitors
Structural highlights
FunctionPublication Abstract from PubMedAutotaxin 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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