7cwa

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==Crystal structure of PDE8A catalytic domain in complex with clofarabine==
==Crystal structure of PDE8A catalytic domain in complex with clofarabine==
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<StructureSection load='7cwa' size='340' side='right'caption='[[7cwa]]' scene=''>
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<StructureSection load='7cwa' size='340' side='right'caption='[[7cwa]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CWA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CWA FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7cwa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CWA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CWA FirstGlance]. <br>
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</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=7cwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cwa OCA], [https://pdbe.org/7cwa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cwa RCSB], [https://www.ebi.ac.uk/pdbsum/7cwa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cwa ProSAT]</span></td></tr>
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</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>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CFB:2-CHLORO-9-(2-DEOXY-2-FLUORO-B+-D-ARABINOFURANOSYL)-9H-PURIN-6-AMINE'>CFB</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7cwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cwa OCA], [https://pdbe.org/7cwa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cwa RCSB], [https://www.ebi.ac.uk/pdbsum/7cwa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cwa ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PDE8A_HUMAN PDE8A_HUMAN] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in maintaining basal levels of the cyclic nucleotide and/or in the cAMP regulation of germ cell development.<ref>PMID:18983167</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7cwa" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Huang Y]]
[[Category: Huang Y]]

Revision as of 16:17, 29 November 2023

Crystal structure of PDE8A catalytic domain in complex with clofarabine

PDB ID 7cwa

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