3ws8: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3ws8]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WS8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WS8 FirstGlance]. <br> | <table><tr><td colspan='2'>[[3ws8]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WS8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WS8 FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=X4C:8-METHYL-6-[2-(5-METHYL-1-PHENYL-1H-BENZIMIDAZOL-2-YL)ETHYL]IMIDAZO[1,5-A]PYRIMIDINE'>X4C</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=X4C:8-METHYL-6-[2-(5-METHYL-1-PHENYL-1H-BENZIMIDAZOL-2-YL)ETHYL]IMIDAZO[1,5-A]PYRIMIDINE'>X4C</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ws9|3ws9]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ws9|3ws9]]</td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ws8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ws8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ws8 RCSB], [http://www.ebi.ac.uk/pdbsum/3ws8 PDBsum]</span></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=3ws8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ws8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ws8 RCSB], [http://www.ebi.ac.uk/pdbsum/3ws8 PDBsum]</span></td></tr> | ||
<table> | </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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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Novel benzimidazole derivatives as phosphodiesterase 10A (PDE10A) inhibitors with improved metabolic stability.,Chino A, Masuda N, Amano Y, Honbou K, Mihara T, Yamazaki M, Tomishima M Bioorg Med Chem. 2014 Jul 1;22(13):3515-26. doi: 10.1016/j.bmc.2014.04.023. Epub , 2014 Apr 20. PMID:24837154<ref>PMID:24837154</ref> | Novel benzimidazole derivatives as phosphodiesterase 10A (PDE10A) inhibitors with improved metabolic stability.,Chino A, Masuda N, Amano Y, Honbou K, Mihara T, Yamazaki M, Tomishima M Bioorg Med Chem. 2014 Jul 1;22(13):3515-26. doi: 10.1016/j.bmc.2014.04.023. Epub , 2014 Apr 20. PMID:24837154<ref>PMID:24837154</ref> | ||
From | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
== References == | == References == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Amano, Y | [[Category: Amano, Y]] | ||
[[Category: Honbou, K | [[Category: Honbou, K]] | ||
[[Category: Hydrolase-hydrolase inhibitor complex]] | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
[[Category: Phosphodiesterase]] | [[Category: Phosphodiesterase]] | ||
Revision as of 10:45, 24 December 2014
Crystal structure of PDE10A in complex with a benzimidazole inhibitorCrystal structure of PDE10A in complex with a benzimidazole inhibitor
Structural highlights
Function[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.[1] Publication Abstract from PubMedIn this study, we report the identification of potent benzimidazoles as PDE10A inhibitors. We first identified imidazopyridine 1 as a high-throughput screening hit compound from an in-house library. Next, optimization of the imidazopyridine moiety to improve inhibitory activity gave imidazopyridinone 10b. Following further structure-activity relationship development by reducing lipophilicity and introducing substituents, we acquired 35, which exhibited both improved metabolic stability and reduced CYP3A4 time-dependent inhibition. Novel benzimidazole derivatives as phosphodiesterase 10A (PDE10A) inhibitors with improved metabolic stability.,Chino A, Masuda N, Amano Y, Honbou K, Mihara T, Yamazaki M, Tomishima M Bioorg Med Chem. 2014 Jul 1;22(13):3515-26. doi: 10.1016/j.bmc.2014.04.023. Epub , 2014 Apr 20. PMID:24837154[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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