6ko0: Difference between revisions

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-'''Unreleased structure'''
-The entry 6ko0 is ON HOLD
+==The crystal structue of PDE10A complexed with 1i==
+<StructureSection load='6ko0' size='340' side='right'caption='[[6ko0]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6ko0]] is a 2 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=6KO0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KO0 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.600029&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DKU:3-[2-(5-methyl-1-phenyl-benzimidazol-2-yl)ethyl]chromen-4-one'>DKU</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6ko0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ko0 OCA], [https://pdbe.org/6ko0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ko0 RCSB], [https://www.ebi.ac.uk/pdbsum/6ko0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ko0 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://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 10 (PDE10) inhibitors have received much attention as promising therapeutic agents for central nervous system (CNS) disorders such as schizophrenia and Huntington's disease. Recently, a hit compound 1 with a novel chromone scaffold has shown moderate inhibitory activity against PDE10A (IC50 = 500 nM). Hit-to-lead optimization has resulted in compound 3e with an improved inhibitory activity (IC50 = 6.5 nM), remarkable selectivity (&gt;95-fold over other PDEs), and good metabolic stability (RLM t1/2 = 105 min) by using an integrated strategy (molecular modeling, chemical synthesis, bioassay, and cocrystal structure). The cocrystal structural information provides insights into the binding pattern of 3e in the PDE10A catalytic domain to highlight the key role of the halogen and hydrogen bonds toward Tyr524 and Tyr693, respectively, thereby resulting in high selectivity against other PDEs. These new observations are of benefit for the rational design of the next generation PDE10 inhibitors for CNS disorders.
-Authors: Huang, Y.-Y., Yu, Y.F., Zhang, C., Guo, L., Wu, D., Luo, H.-B.
+Discovery and Optimization of Chromone Derivatives as Novel Selective Phosphodiesterase 10 Inhibitors.,Yu YF, Zhang C, Huang YY, Zhang S, Zhou Q, Li X, Lai Z, Li Z, Gao Y, Wu Y, Guo L, Wu D, Luo HB ACS Chem Neurosci. 2020 Mar 11. doi: 10.1021/acschemneuro.0c00024. PMID:32105440<ref>PMID:32105440</ref>
-Description: The crystal structue of PDE10A complexed with 1i
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Luo, H.-B]]
+<div class="pdbe-citations 6ko0" style="background-color:#fffaf0;"></div>
-[[Category: Yu, Y.F]]
-[[Category: Wu, D]]
+==See Also==
-[[Category: Guo, L]]
+*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
-[[Category: Zhang, C]]
+== References ==
-[[Category: Huang, Y.-Y]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Guo L]]
+[[Category: Huang Y-Y]]
+[[Category: Luo H-B]]
+[[Category: Wu D]]
+[[Category: Yu YF]]
+[[Category: Zhang C]]