5b25
From Proteopedia
(Difference between revisions)
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| - | ''' | + | ==Crystal structure of human PDE1B with inhibitor 3== |
| + | <StructureSection load='5b25' size='340' side='right' caption='[[5b25]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5b25]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5B25 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5B25 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4QJ:(11R,15S)-4-{[4-(6-FLUOROPYRIDIN-2-YL)PHENYL]METHYL}-8-METHYL-5-(PHENYLAMINO)-1,3,4,8,10-PENTAAZATETRACYCLO[7.6.0.02,6.011,15]PENTADECA-2,5,9-TRIEN-7-ONE'>4QJ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5b25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b25 OCA], [http://pdbe.org/5b25 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5b25 RCSB], [http://www.ebi.ac.uk/pdbsum/5b25 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/PDE1B_HUMAN PDE1B_HUMAN]] Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a preference for cGMP as a substrate. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A diverse set of 3-aminopyrazolo[3,4-d]pyrimidinones was designed and synthesized. The structure-activity relationships of these polycyclic compounds as phosphodiesterase 1 (PDE1) inhibitors were studied along with their physicochemical and pharmacokinetic properties. Systematic optimizations of this novel scaffold culminated in the identification of a clinical candidate, (6aR,9aS)-2-(4-(6-fluoropyridin-2-yl)benzyl)-5-methyl-3-(phenylamino)-5,6a,7,8,9, 9a-hexahydrocyclopenta[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4-(2H)-one phosphate (ITI-214), which exhibited picomolar inhibitory potency for PDE1, demonstrated excellent selectivity against all other PDE families and showed good efficacy in vivo. Currently, this investigational new drug is in Phase I clinical development and being considered for the treatment of several indications including cognitive deficits associated with schizophrenia and Alzheimer's disease, movement disorders, attention deficit and hyperactivity disorders, and other central nervous system (CNS) and non-CNS disorders. | ||
| - | + | Discovery of Potent and Selective Inhibitors of Phosphodiesterase 1 for the Treatment of Cognitive Impairment Associated with Neurodegenerative and Neuropsychiatric Diseases.,Li P, Zheng H, Zhao J, Zhang L, Yao W, Zhu H, Beard JD, Ida K, Lane W, Snell G, Sogabe S, Heyser CJ, Snyder GL, Hendrick JP, Vanover KE, Davis RE, Wennogle LP J Med Chem. 2016 Feb 2. PMID:26789933<ref>PMID:26789933</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 5b25" style="background-color:#fffaf0;"></div> | |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: 3',5'-cyclic-nucleotide phosphodiesterase]] | ||
| + | [[Category: Ida, K]] | ||
| + | [[Category: Lane, W]] | ||
[[Category: Snell, G]] | [[Category: Snell, G]] | ||
| - | [[Category: Lane, W]] | ||
| - | [[Category: Ida, K]] | ||
[[Category: Sogabe, S]] | [[Category: Sogabe, S]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
| + | [[Category: Inhibitor]] | ||
Revision as of 15:41, 3 February 2016
Crystal structure of human PDE1B with inhibitor 3
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