7cwg: Difference between revisions

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-'''Unreleased structure'''
-The entry 7cwg is ON HOLD  until Paper Publication
+==Crystal structure of PDE8A catalytic domain in complex with 3a==
+<StructureSection load='7cwg' size='340' side='right'caption='[[7cwg]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+== Structural highlights ==
+<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]] 2.8&#8491;</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>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+To 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.
-Authors: Huang, Y., Wu, X.-N., Zhou, Q., Wu, Y., Luo, H.-B.
+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<ref>PMID:33291877</ref>
-Description: Crystal structure of PDE8A catalytic domain in complex with 3a
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Luo, H.-B]]
+<div class="pdbe-citations 7cwg" style="background-color:#fffaf0;"></div>
-[[Category: Zhou, Q]]
-[[Category: Wu, Y]]
+==See Also==
-[[Category: Wu, X.-N]]
+*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
-[[Category: Huang, Y]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Huang Y]]
+[[Category: Luo H-B]]
+[[Category: Wu X-N]]
+[[Category: Wu Y]]
+[[Category: Zhou Q]]