6b96: Difference between revisions
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<StructureSection load='6b96' size='340' side='right' caption='[[6b96]], [[Resolution|resolution]] 1.88Å' scene=''> | <StructureSection load='6b96' size='340' side='right' caption='[[6b96]], [[Resolution|resolution]] 1.88Å' scene=''> | ||
== Structural highlights == | == 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> | <table><tr><td colspan='2'>[[6b96]] is a 2 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=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> | </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='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='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> | <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> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]] | [[Category: 3',5'-cyclic-nucleotide phosphodiesterase]] | ||
[[Category: Human]] | |||
[[Category: Lu, J]] | [[Category: Lu, J]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Phosphodiesterase 2]] | [[Category: Phosphodiesterase 2]] | ||
Revision as of 10:44, 29 November 2017
Crystal Structure of PDE2 in complex with compound 16Crystal Structure of PDE2 in complex with compound 16
Structural highlights
Function[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.[1] [2] Publication Abstract from PubMedWe 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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