3F7Z

X-ray Co-Crystal Structure of Glycogen Synthase Kinase 3beta in Complex with an Inhibitor

Summary for 3F7Z

• Entry DOI: 10.2210/pdb3f7z/pdb
• Descriptor: Glycogen synthase kinase-3 beta, 2-(1,3-benzodioxol-5-yl)-5-[(3-fluoro-4-methoxybenzyl)sulfanyl]-1,3,4-oxadiazole (3 entities in total)
• Functional Keywords: enzyme, protein kinase, inhibitor co-crystal structure, atp-binding, kinase, nucleotide-binding, phosphoprotein, serine/threonine-protein kinase, transferase, wnt signaling pathway
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P49841
• Total number of polymer chains: 2
• Total formula weight: 80486.27

Authors

Mol, C.D.,Dougan, D.R. (deposition date: 2008-11-10, release date: 2009-03-10, Last modification date: 2024-11-27)

Primary citation

Saitoh, M.,Kunitomo, J.,Kimura, E.,Hayase, Y.,Kobayashi, H.,Uchiyama, N.,Kawamoto, T.,Tanaka, T.,Mol, C.D.,Dougan, D.R.,Textor, G.S.,Snell, G.P.,Itoh, F.
Design, synthesis and structure-activity relationships of 1,3,4-oxadiazole derivatives as novel inhibitors of glycogen synthase kinase-3beta.
Bioorg.Med.Chem., 17:2017-2029, 2009

PubMed Abstract: Glycogen synthase kinase-3beta (GSK-3beta) is implicated in abnormal hyperphosphorylation of tau protein and its inhibitors are expected to be a promising therapeutic agents for the treatment of Alzheimer's disease. Here we report design, synthesis and structure-activity relationships of a novel series of oxadiazole derivatives as GSK-3beta inhibitors. Among these inhibitors, compound 20x showed highly selective and potent GSK-3beta inhibitory activity in vitro and its binding mode was determined by obtaining the X-ray co-crystal structure of 20x and GSK-3beta.

PubMed: 19200745
DOI: 10.1016/j.bmc.2009.01.019

Experimental method

X-RAY DIFFRACTION (2.4 Å)