6kdz
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of PDE10A in complex with a triazolopyrimidine inhibitor== | |
| + | <StructureSection load='6kdz' size='340' side='right'caption='[[6kdz]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6kdz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KDZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KDZ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D79:4-[2-(5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)ethyl]-3,7,8,10-tetrazatricyclo[7.4.0.0^{2,7}]trideca-1,3,5,8,10,12-hexaen-6-ol'>D79</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">[[6kdx|6kdx]]</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=6kdz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kdz OCA], [http://pdbe.org/6kdz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kdz RCSB], [http://www.ebi.ac.uk/pdbsum/6kdz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kdz ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/PDE10_HUMAN PDE10_HUMAN]] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:17389385</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Phosphodiesterase 10A (PDE10A) inhibitors were designed and synthesized based on the dihydro-imidazobenzimidazole scaffold. Compound 5a showed moderate inhibitory activity and good permeability, but unfavorable high P-glycoprotein (P-gp) liability for brain penetration. We performed an optimization study to improve both the P-gp efflux ratio and PDE10A inhibitory activity. As a result, 6d was identified with improved P-gp liability and high PDE10A inhibitory activity. Compound 6d also showed satisfactory brain penetration, suppressed phencyclidine-induced hyperlocomotion and improved MK-801-induced working memory deficit. | ||
| - | + | Synthesis, SAR study, and biological evaluation of novel 2,3-dihydro-1H-imidazo[1,2-a]benzimidazole derivatives as phosphodiesterase 10A inhibitors.,Chino A, Honda S, Morita M, Yonezawa K, Hamaguchi W, Amano Y, Moriguchi H, Yamazaki M, Aota M, Tomishima M, Masuda N Bioorg Med Chem. 2019 Aug 15;27(16):3692-3706. doi: 10.1016/j.bmc.2019.07.010., Epub 2019 Jul 6. PMID:31301949<ref>PMID:31301949</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6kdz" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Amano, Y]] | [[Category: Amano, Y]] | ||
[[Category: Honbou, K]] | [[Category: Honbou, K]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Inhibitor]] | ||
Revision as of 16:35, 14 August 2019
Crystal structure of PDE10A in complex with a triazolopyrimidine inhibitor
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