7cwg: Difference between revisions
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<StructureSection load='7cwg' size='340' side='right'caption='[[7cwg]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='7cwg' size='340' side='right'caption='[[7cwg]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CWG 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]] 2.8Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GJU:9-[(1~{S})-1-[4-[2,2-bis(fluoranyl)ethoxy]pyridin-2-yl]ethyl]-2-chloranyl-purin-6-amine'>GJU</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GJU:9-[(1~{S})-1-[4-[2,2-bis(fluoranyl)ethoxy]pyridin-2-yl]ethyl]-2-chloranyl-purin-6-amine'>GJU</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7cwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cwg OCA], [https://pdbe.org/7cwg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cwg RCSB], [https://www.ebi.ac.uk/pdbsum/7cwg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cwg ProSAT]</span></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=7cwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cwg OCA], [https://pdbe.org/7cwg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cwg RCSB], [https://www.ebi.ac.uk/pdbsum/7cwg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cwg ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Huang Y]] | [[Category: Huang Y]] | ||
Latest revision as of 11:39, 17 October 2024
Crystal structure of PDE8A catalytic domain in complex with 3aCrystal structure of PDE8A catalytic domain in complex with 3a
Structural highlights
Publication Abstract from PubMedTo validate the hypothesis that Tyr748 is a crucial residue to aid the discovery of highly selective phosphodiesterase 8A (PDE8A) inhibitors, we identified a series of 2-chloroadenine derivatives based on the hit clofarabine. Structure-based design targeting Tyr748 in PDE8 resulted in the lead compound 3a (IC50 = 0.010 muM) with high selectivity with a reasonable druglike profile. In the X-ray crystal structure, 3a bound to PDE8A with a different mode from 3-isobutyl-1-methylxanthine (a pan-PDE inhibitor) and gave a H-bond of 2.7 A with Tyr748, which possibly interprets the 220-fold selectivity of 3a against PDE2A. Additionally, oral administration of compound 3a achieved remarkable therapeutic effects against vascular dementia (VaD), indicating that PDE8 inhibitors could serve as potential anti-VaD agents. Rational Design of 2-Chloroadenine Derivatives as Highly Selective Phosphodiesterase 8A Inhibitors.,Huang Y, Wu XN, Zhou Q, Wu Y, Zheng D, Li Z, Guo L, Luo HB J Med Chem. 2020 Dec 24;63(24):15852-15863. doi: 10.1021/acs.jmedchem.0c01573., Epub 2020 Dec 8. PMID:33291877[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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