5uoy
From Proteopedia
(Difference between revisions)
m (Protected "5uoy" [edit=sysop:move=sysop]) |
|||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human PDE1B catalytic domain in complex with inhibitor 16j (6-(4-Methoxybenzyl)-9-((tetrahydro-2H-pyran-4-yl)methyl)-8,9,10,11-tetrahydropyrido[4',3':4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one)== | |
| + | <StructureSection load='5uoy' size='340' side='right' caption='[[5uoy]], [[Resolution|resolution]] 1.82Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5uoy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UOY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UOY FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8HM:6-[(4-METHOXYPHENYL)METHYL]-9-[(OXAN-4-YL)METHYL]-8,9,10,11-TETRAHYDROPYRIDO[4,3 4,5]THIENO[3,2-E][1,2,4]TRIAZOLO[1,5-C]PYRIMIDIN-5(6H)-ONE'>8HM</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">[[5up0|5up0]]</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=5uoy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uoy OCA], [http://pdbe.org/5uoy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uoy RCSB], [http://www.ebi.ac.uk/pdbsum/5uoy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uoy ProSAT]</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 series of potent thienotriazolopyrimidinone-based PDE1 inhibitors was discovered. X-ray crystal structures of example compounds from this series in complex with the catalytic domain of PDE1B and PDE10A were determined, allowing optimization of PDE1B potency and PDE selectivity. Reduction of hERG affinity led to greater than a 3000-fold selectivity for PDE1B over hERG. 6-(4-Methoxybenzyl)-9-((tetrahydro-2H-pyran-4-yl)methyl)-8,9,10,11-tetrahydropyri do[4',3':4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one was identified as an orally bioavailable and brain penetrating PDE1B enzyme inhibitor with potent memory-enhancing effects in a rat model of object recognition memory. | ||
| - | + | Discovery of Selective Phosphodiesterase 1 Inhibitors with Memory Enhancing Properties.,Dyck B, Branstetter B, Gharbaoui T, Hudson AR, Breitenbucher JG, Gomez L, Botrous I, Marrone T, Barido R, Allerston CK, Cedervall EP, Xu R, Sridhar V, Barker R, Aertgeerts K, Schmelzer K, Neul D, Lee D, Massari ME, Andersen CB, Sebring K, Zhou X, Petroski R, Limberis J, Augustin M, Chun LE, Edwards TE, Peters M, Tabatabaei A J Med Chem. 2017 Apr 13. doi: 10.1021/acs.jmedchem.7b00302. PMID:28406621<ref>PMID:28406621</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Cedervall, E | + | <div class="pdbe-citations 5uoy" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: 3',5'-cyclic-nucleotide phosphodiesterase]] | ||
| + | [[Category: Aertgeerts, K]] | ||
| + | [[Category: Allerston, C K]] | ||
| + | [[Category: Barker, R]] | ||
| + | [[Category: Cedervall, E P]] | ||
| + | [[Category: Sridhar, V]] | ||
| + | [[Category: Xu, R]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Hydrolase inhibitor]] | ||
| + | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
Revision as of 13:55, 27 April 2017
Crystal structure of human PDE1B catalytic domain in complex with inhibitor 16j (6-(4-Methoxybenzyl)-9-((tetrahydro-2H-pyran-4-yl)methyl)-8,9,10,11-tetrahydropyrido[4',3':4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one)
| |||||||||||
