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{{STRUCTURE_4htx| PDB=4htx | SCENE= }}
==Crystal structure of PDE2 catalytic domain in complex with BAY60-7550==
===Crystal structure of PDE2 catalytic domain in complex with BAY60-7550===
<StructureSection load='4htx' size='340' side='right' caption='[[4htx]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
{{ABSTRACT_PUBMED_23899287}}
== Structural highlights ==
<table><tr><td colspan='2'>[[4htx]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HTX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HTX FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=19F:2-(3,4-DIMETHOXYBENZYL)-7-[(2R,3R)-2-HYDROXY-6-PHENYLHEXAN-3-YL]-5-METHYLIMIDAZO[5,1-F][1,2,4]TRIAZIN-4(3H)-ONE'>19F</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4htz|4htz]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDE2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<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>
<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=4htx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4htx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4htx RCSB], [http://www.ebi.ac.uk/pdbsum/4htx PDBsum]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
To better understand the structural origins of inhibitor selectivity of human phosphodieasterase families (PDEs 1-11), here we report the X-ray crystal structure of PDE2 in complex with a highly selective, nanomolar inhibitor (BAY60-7550) at 1.9 A resolution, and the structure of apo PDE2 at 2.0 A resolution. The crystal structures reveal that the inhibitor binds to the PDE2 active site by using not only the conserved glutamine-switch mechanism for substrate binding, but also a binding-induced, hydrophobic pocket that was not reported previously. In silico affinity profiling by molecular docking indicates that the inhibitor binding to this pocket contributes significantly to the binding affinity and thereby improves the inhibitor selectivity for PDE2. Our results highlight a structure-based design strategy that exploits the potential binding-induced pockets to achieve higher selectivity in the PDE inhibitor development.


==Function==
X-ray Crystal Structure of Phosphodiesterase 2 in Complex with a Highly Selective, Nanomolar Inhibitor Reveals a Binding-Induced Pocket Important for Selectivity.,Zhu J, Yang Q, Dai D, Huang Q J Am Chem Soc. 2013 Aug 14;135(32):11708-11. doi: 10.1021/ja404449g. Epub 2013, Aug 2. PMID:23899287<ref>PMID:23899287</ref>
[[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>


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[4htx]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HTX OCA].
</div>


==Reference==
==See Also==
<ref group="xtra">PMID:023899287</ref><references group="xtra"/><references/>
*[[Phosphodiesterase|Phosphodiesterase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Huang, Q.]]
[[Category: Huang, Q]]
[[Category: Zhu, J.]]
[[Category: Zhu, J]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
Retrieved from "https://proteopedia.org/4htx"