5up0 | pdb_00005up0

Crystal structure of human PDE1B catalytic domain in complex with inhibitor 3 (6-(4-chlorobenzyl)-8,9,10,11-tetrahydrobenzo[4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one)

spinqualitylabelsall models 5up0, resolution 2.04Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5up0 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.04Å Ligands: 8HP, MG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphodiesterase 3D structures

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