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| | <StructureSection load='5up0' size='340' side='right'caption='[[5up0]], [[Resolution|resolution]] 2.04Å' scene=''> | | <StructureSection load='5up0' size='340' side='right'caption='[[5up0]], [[Resolution|resolution]] 2.04Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5up0]] is a 1 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=5UP0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5UP0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5up0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UP0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UP0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8HP:6-[(4-CHLOROPHENYL)METHYL]-8,9,10,11-TETRAHYDRO[1]BENZOTHIENO[3,2-E][1,2,4]TRIAZOLO[1,5-C]PYRIMIDIN-5(6H)-ONE'>8HP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.04Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5uoy|5uoy]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8HP:6-[(4-CHLOROPHENYL)METHYL]-8,9,10,11-TETRAHYDRO[1]BENZOTHIENO[3,2-E][1,2,4]TRIAZOLO[1,5-C]PYRIMIDIN-5(6H)-ONE'>8HP</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">PDE1B, PDE1B1, PDES1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5up0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5up0 OCA], [https://pdbe.org/5up0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5up0 RCSB], [https://www.ebi.ac.uk/pdbsum/5up0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5up0 ProSAT]</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://proteopedia.org/fgij/fg.htm?mol=5up0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5up0 OCA], [http://pdbe.org/5up0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5up0 RCSB], [http://www.ebi.ac.uk/pdbsum/5up0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5up0 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == 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. | + | [https://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 3',5'-cyclic-nucleotide phosphodiesterase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Aertgeerts, K]] | + | [[Category: Aertgeerts K]] |
| - | [[Category: Allerston, C K]] | + | [[Category: Allerston CK]] |
| - | [[Category: Barker, R]] | + | [[Category: Barker R]] |
| - | [[Category: Cedervall, E P]] | + | [[Category: Cedervall EP]] |
| - | [[Category: Sridhar, V]] | + | [[Category: Sridhar V]] |
| - | [[Category: Xu, R]] | + | [[Category: Xu R]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase inhibitor]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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. Discovery of Selective Phosphodiesterase 1 Inhibitors with Memory Enhancing Properties. J Med Chem. 2017 Apr 13. doi: 10.1021/acs.jmedchem.7b00302. PMID:28406621 doi:http://dx.doi.org/10.1021/acs.jmedchem.7b00302
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