7p0k
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Autotaxin (ENPP2) with 18F-labeled positron emission tomography ligand== | |
| + | <StructureSection load='7p0k' size='340' side='right'caption='[[7p0k]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7p0k]] 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=7P0K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P0K 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]] 2.2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4I0:2-[[2-ethyl-6-[4-[2-[(3~{R})-3-fluoranylpyrrolidin-1-yl]-2-oxidanylidene-ethyl]piperazin-1-yl]imidazo[1,2-a]pyridin-3-yl]-methyl-amino]-4-(4-fluorophenyl)-2,3-dihydro-1,3-thiazole-5-carbonitrile'>4I0</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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=7p0k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p0k OCA], [https://pdbe.org/7p0k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p0k RCSB], [https://www.ebi.ac.uk/pdbsum/7p0k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p0k 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 (ATX) is a secreted phosphodiesterase that has been implicated in a remarkably wide array of pathologies, especially in fibrosis and cancer. While ATX inhibitors have entered the clinical arena, a validated probe for positron emission tomography (PET) is currently lacking. With the aim to develop a suitable ATX-targeted PET radioligand, we have synthesized a focused library of fluorinated imidazo[1,2-a]pyridine derivatives, determined their inhibition constants, and confirmed their binding mode by crystallographic analysis. Based on their promising in vitro properties, compounds 9c, 9f, 9h, and 9j were radiofluorinated. Also, a deuterated analog of [(18)F]9j, designated as [(18)F]ATX-1905 ([(18)F]20), was designed and proved to be highly stable against in vivo radiodefluorination compared with [(18)F]9c, [(18)F]9f, [(18)F]9h, and [(18)F]9j. These results along with in vitro and in vivo studies toward ATX in a mouse model of LPS-induced liver injury suggest that [(18)F]ATX-1905 is a suitable PET probe for the non-invasive quantification of ATX. | ||
| - | + | Imaging Autotaxin In Vivo with (18)F-Labeled Positron Emission Tomography Ligands.,Deng X, Salgado-Polo F, Shao T, Xiao Z, Van R, Chen J, Rong J, Haider A, Shao Y, Josephson L, Perrakis A, Liang SH J Med Chem. 2021 Oct 28;64(20):15053-15068. doi: 10.1021/acs.jmedchem.1c00913. , Epub 2021 Oct 18. PMID:34662125<ref>PMID:34662125</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 7p0k" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: Josephson | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Shao | + | [[Category: Chen J]] |
| - | [[Category: | + | [[Category: Haider A]] |
| - | [[Category: | + | [[Category: Josephson L]] |
| - | [[Category: | + | [[Category: Liang SH]] |
| + | [[Category: Perrakis A]] | ||
| + | [[Category: Rong J]] | ||
| + | [[Category: Salgado-Polo F]] | ||
| + | [[Category: Shao T]] | ||
| + | [[Category: Shao Y]] | ||
| + | [[Category: Van R]] | ||
| + | [[Category: Xiao Z]] | ||
Current revision
Crystal structure of Autotaxin (ENPP2) with 18F-labeled positron emission tomography ligand
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Categories: Large Structures | Rattus norvegicus | Chen J | Haider A | Josephson L | Liang SH | Perrakis A | Rong J | Salgado-Polo F | Shao T | Shao Y | Van R | Xiao Z
