4zo5: Difference between revisions
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<StructureSection load='4zo5' size='340' side='right'caption='[[4zo5]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='4zo5' size='340' side='right'caption='[[4zo5]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4zo5]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4zo5]] 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=4ZO5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZO5 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4PX:3-(1-HYDROXY-2-METHYLPROPAN-2-YL)-5-PHENYL-3,5-DIHYDRO-1H-IMIDAZO[4,5-C][1,8]NAPHTHYRIDINE-2,4-DIONE'>4PX</scene>, <scene name='pdbligand=4Q0:2-{2-[3-(4-METHOXYPHENYL)-4-OXO-3,4-DIHYDROQUINAZOLIN-2-YL]ETHYL}-4-(PROPAN-2-YLOXY)-1H-ISOINDOLE-1,3(2H)-DIONE'>4Q0</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4PX:3-(1-HYDROXY-2-METHYLPROPAN-2-YL)-5-PHENYL-3,5-DIHYDRO-1H-IMIDAZO[4,5-C][1,8]NAPHTHYRIDINE-2,4-DIONE'>4PX</scene>, <scene name='pdbligand=4Q0:2-{2-[3-(4-METHOXYPHENYL)-4-OXO-3,4-DIHYDROQUINAZOLIN-2-YL]ETHYL}-4-(PROPAN-2-YLOXY)-1H-ISOINDOLE-1,3(2H)-DIONE'>4Q0</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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4zo5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zo5 OCA], [https://pdbe.org/4zo5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zo5 RCSB], [https://www.ebi.ac.uk/pdbsum/4zo5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zo5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 21: | Line 21: | ||
==See Also== | ==See Also== | ||
*[[Phosphodiesterase|Phosphodiesterase]] | *[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Yan | [[Category: Yan Y]] | ||
Latest revision as of 11:21, 27 September 2023
PDE10 complexed with 4-isopropoxy-2-(2-(3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)isoindoline-1,3-dionePDE10 complexed with 4-isopropoxy-2-(2-(3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)isoindoline-1,3-dione
Structural highlights
FunctionPDE10_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.[1] Publication Abstract from PubMedPhosphodiesterase 10A (PDE10A) inhibition has recently been identified as a potential mechanism to treat multiple symptoms that manifest in schizophrenia. In order to facilitate preclinical development and support key proof-of-concept clinical trials of novel PDE10A inhibitors, it is critical to discover positron emission tomography (PET) tracers that enable plasma concentration/PDE10A occupancy relationships to be established across species with structurally diverse PDE10A inhibitors. In this Letter, we describe how a high-throughput screening hit was optimized to provide [11C]MK-8193 (8j), a PET tracer that supports the determination of plasma concentration/PDE10A occupancy relationships for structurally diverse series of PDE10A inhibitors in both rat and rhesus monkey. Discovery of [C]MK-8193 as a PET tracer to measure target engagement of phosphodiesterase 10A (PDE10A) inhibitors.,Cox CD, Hostetler ED, Flores BA, Evelhoch JL, Fan H, Gantert L, Holahan M, Eng W, Joshi A, McGaughey G, Meng X, Purcell M, Raheem IT, Riffel K, Yan Y, Renger JJ, Smith SM, Coleman PJ Bioorg Med Chem Lett. 2015 Jun 1. pii: S0960-894X(15)00554-5. doi:, 10.1016/j.bmcl.2015.05.080. PMID:26077491[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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