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==Crystal Structure of PDE10A with a biaryl ether inhibitor ((1-(3-(4-((1H-benzo[d]imidazol-2-yl)amino)phenoxy)pyridin-2-yl)piperidin-4-yl)methanol)== | |||
<StructureSection load='4heu' size='340' side='right'caption='[[4heu]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4heu]] 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=4HEU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HEU 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]] 2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=15J:(1-{3-[4-(1H-BENZIMIDAZOL-2-YLAMINO)PHENOXY]PYRIDIN-2-YL}PIPERIDIN-4-YL)METHANOL'>15J</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4heu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4heu OCA], [https://pdbe.org/4heu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4heu RCSB], [https://www.ebi.ac.uk/pdbsum/4heu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4heu 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 == | |||
We report the discovery of a novel series of biaryl ethers as potent and selective PDE10A inhibitors. Structure-activity studies improved the potency and decreased Pgp-mediated efflux found in the initial compound 4. X-ray crystallographic studies revealed two novel binding modes to the catalytic site of the PDE10A enzyme. | |||
Discovery of selective biaryl ethers as PDE10A inhibitors: Improvement in potency and mitigation of Pgp-mediated efflux.,Rzasa RM, Hu E, Rumfelt S, Chen N, Andrews KL, Chmait S, Falsey JR, Zhong W, Jones AD, Porter A, Louie SW, Zhao X, Treanor JJ, Allen JR Bioorg Med Chem Lett. 2012 Dec 15;22(24):7371-5. doi: 10.1016/j.bmcl.2012.10.078., Epub 2012 Oct 22. PMID:23149228<ref>PMID:23149228</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4heu" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
[[ | *[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Chmait S]] | ||
[[Category: | [[Category: Jordan S]] | ||
Latest revision as of 10:01, 27 November 2024
Crystal Structure of PDE10A with a biaryl ether inhibitor ((1-(3-(4-((1H-benzo[d]imidazol-2-yl)amino)phenoxy)pyridin-2-yl)piperidin-4-yl)methanol)Crystal Structure of PDE10A with a biaryl ether inhibitor ((1-(3-(4-((1H-benzo[d]imidazol-2-yl)amino)phenoxy)pyridin-2-yl)piperidin-4-yl)methanol)
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 PubMedWe report the discovery of a novel series of biaryl ethers as potent and selective PDE10A inhibitors. Structure-activity studies improved the potency and decreased Pgp-mediated efflux found in the initial compound 4. X-ray crystallographic studies revealed two novel binding modes to the catalytic site of the PDE10A enzyme. Discovery of selective biaryl ethers as PDE10A inhibitors: Improvement in potency and mitigation of Pgp-mediated efflux.,Rzasa RM, Hu E, Rumfelt S, Chen N, Andrews KL, Chmait S, Falsey JR, Zhong W, Jones AD, Porter A, Louie SW, Zhao X, Treanor JJ, Allen JR Bioorg Med Chem Lett. 2012 Dec 15;22(24):7371-5. doi: 10.1016/j.bmcl.2012.10.078., Epub 2012 Oct 22. PMID:23149228[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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