3ws9
From Proteopedia
(Difference between revisions)
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==Crystal structure of PDE10A in complex with a benzimdazole inhibitor== | ==Crystal structure of PDE10A in complex with a benzimdazole inhibitor== | ||
| - | <StructureSection load='3ws9' size='340' side='right'caption='[[3ws9]]' scene=''> | + | <StructureSection load='3ws9' size='340' side='right'caption='[[3ws9]], [[Resolution|resolution]] 2.99Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WS9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WS9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ws9]] 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=3WS9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WS9 FirstGlance]. <br> |
| - | </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=3ws9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ws9 OCA], [https://pdbe.org/3ws9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ws9 RCSB], [https://www.ebi.ac.uk/pdbsum/3ws9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ws9 ProSAT]</span></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]] 2.99Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=X4D:7-[2-(5-METHYL-1-PHENYL-1H-BENZIMIDAZOL-2-YL)ETHYL]IMIDAZO[1,5-B]PYRIDAZINE'>X4D</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=3ws9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ws9 OCA], [https://pdbe.org/3ws9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ws9 RCSB], [https://www.ebi.ac.uk/pdbsum/3ws9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ws9 ProSAT]</span></td></tr> | ||
</table> | </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 == | ||
| + | In 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<ref>PMID:24837154</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 3ws9" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] | *[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Amano Y]] | [[Category: Amano Y]] | ||
[[Category: Honbou K]] | [[Category: Honbou K]] | ||
Current revision
Crystal structure of PDE10A in complex with a benzimdazole inhibitor
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