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4d08

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==PDE2a catalytic domain in complex with a brain penetrant inhibitor==
==PDE2a catalytic domain in complex with a brain penetrant inhibitor==
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<StructureSection load='4d08' size='340' side='right' caption='[[4d08]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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<StructureSection load='4d08' size='340' side='right'caption='[[4d08]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4d08]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4D08 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4D08 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4d08]] is a 4 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=4D08 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4D08 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=Q2T:1-(5-BUTOXYPYRIDIN-3-YL)-4-METHYL-8-(MORPHOLIN-4-YLMETHYL)[1,2,4]TRIAZOLO[4,3-A]QUINOXALINE'>Q2T</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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]] 1.9&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4d09|4d09]]</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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=Q2T:1-(5-BUTOXYPYRIDIN-3-YL)-4-METHYL-8-(MORPHOLIN-4-YLMETHYL)[1,2,4]TRIAZOLO[4,3-A]QUINOXALINE'>Q2T</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.17 3.1.4.17] </span></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=4d08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d08 OCA], [https://pdbe.org/4d08 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4d08 RCSB], [https://www.ebi.ac.uk/pdbsum/4d08 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4d08 ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4d08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d08 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4d08 RCSB], [http://www.ebi.ac.uk/pdbsum/4d08 PDBsum]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/PDE2A_HUMAN PDE2A_HUMAN]] Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.<ref>PMID:15938621</ref> <ref>PMID:19828435</ref>
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[https://www.uniprot.org/uniprot/PDE2A_HUMAN PDE2A_HUMAN] Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.<ref>PMID:15938621</ref> <ref>PMID:19828435</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Structure-guided design led to the identification of the novel, potent, and selective phosphodiesterase 2 (PDE2) inhibitor 12. Compound 12 demonstrated a &gt;210-fold selectivity versus PDE10 and PDE11 and was inactive against all other PDE family members up to 10 muM. In vivo evaluation of 12 provided evidence that it is able to engage the target and to increase cGMP levels in relevant brain regions. Hence, 12 is a valuable tool compound for the better understanding of the role of PDE2 in cognitive impairment and other central nervous system related disorders.
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Structure-Based Design of a Potent, Selective, and Brain Penetrating PDE2 Inhibitor with Demonstrated Target Engagement.,Buijnsters P, De Angelis M, Langlois X, Rombouts FJ, Sanderson W, Tresadern G, Ritchie A, Trabanco AA, VanHoof G, Roosbroeck YV, Andres JI ACS Med Chem Lett. 2014 Jul 22;5(9):1049-53. doi: 10.1021/ml500262u. eCollection , 2014 Sep 11. PMID:25221665<ref>PMID:25221665</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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==See Also==
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</div>
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*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
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[[Category: Homo sapiens]]
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[[Category: Andres, J I]]
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[[Category: Large Structures]]
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[[Category: Buijnsters, P]]
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[[Category: Andres JI]]
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[[Category: DeAngelis, M]]
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[[Category: Buijnsters P]]
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[[Category: Langlois, X]]
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[[Category: DeAngelis M]]
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[[Category: Rombouts, F]]
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[[Category: Langlois X]]
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[[Category: Sanderson, W]]
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[[Category: Rombouts F]]
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[[Category: Trabanco, A]]
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[[Category: Sanderson W]]
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[[Category: Tresadern, G]]
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[[Category: Trabanco A]]
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[[Category: VanHoof, G]]
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[[Category: Tresadern G]]
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[[Category: VanRoosbroeck, Y]]
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[[Category: VanHoof G]]
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[[Category: Animal]]
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[[Category: VanRoosbroeck Y]]
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[[Category: Binding site]]
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[[Category: Catalytic domain]]
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[[Category: Cyclic nucleotide phosphodiesterase]]
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[[Category: Disease model]]
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[[Category: Drug evaluation]]
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[[Category: Hydrolase]]
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[[Category: Phosphodiesterase 2 inhibitor]]
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[[Category: Phosphodiesterase inhibitor]]
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[[Category: Preclinical]]
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[[Category: Protein binding]]
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[[Category: Structure-activity relationship]]
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[[Category: Type 2]]
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[[Category: Type 4]]
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Current revision

PDE2a catalytic domain in complex with a brain penetrant inhibitor

PDB ID 4d08

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