6b96: Difference between revisions
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==Crystal Structure of PDE2 in complex with compound 16== | |||
<StructureSection load='6b96' size='340' side='right' caption='[[6b96]], [[Resolution|resolution]] 1.88Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6b96]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B96 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B96 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CZV:6-chloro-N-{1-[4-(trifluoromethyl)phenyl]cyclopropyl}-1H-pyrazolo[3,4-d]pyrimidin-4-amine'>CZV</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6b96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b96 OCA], [http://pdbe.org/6b96 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b96 RCSB], [http://www.ebi.ac.uk/pdbsum/6b96 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b96 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We have identified a novel PDE2 inhibitor series using fragment-based screening. Pyrazolopyrimidine fragment 1, while possessing weak potency (Ki=22.4muM), exhibited good binding efficiencies (LBE=0.49, LLE=4.48) to serve as a start for structure-based drug design. With the assistance of molecular modeling and X-ray crystallography, this fragment was developed into a series of potent PDE2 inhibitors with good physicochemical properties. Compound 16, a PDE2 selective inhibitor, was identified that exhibited favorable rat pharmacokinetic properties. | |||
The identification of a novel lead class for phosphodiesterase 2 inhibition by fragment-based drug design.,Forster AB, Abeywickrema P, Bunda J, Cox CD, Cabalu TD, Egbertson M, Fay J, Getty K, Hall D, Kornienko M, Lu J, Parthasarathy G, Reid J, Sharma S, Shipe WD, Smith SM, Soisson S, Stachel SJ, Su HP, Wang D, Berger R Bioorg Med Chem Lett. 2017 Dec 1;27(23):5167-5171. doi:, 10.1016/j.bmcl.2017.10.054. Epub 2017 Oct 23. PMID:29113762<ref>PMID:29113762</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6b96" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]] | |||
[[Category: Lu, J]] | [[Category: Lu, J]] | ||
[[Category: Hydrolase]] | |||
[[Category: Phosphodiesterase 2]] | |||
