1UV5

GLYCOGEN SYNTHASE KINASE 3 BETA COMPLEXED WITH 6-BROMOINDIRUBIN-3'-OXIME

Summary for 1UV5

• Entry DOI: 10.2210/pdb1uv5/pdb
• Related: 1GNG 1H8F 1I09 1J1B 1J1C 1O6K 1O6L 1O9U 1PYX 1Q3D 1Q3W 1Q41 1Q4L
• Descriptor: GLYCOGEN SYNTHASE KINASE-3 BETA, 6-BROMOINDIRUBIN-3'-OXIME, PHOSPHATE ION, ... (6 entities in total)
• Functional Keywords: transferase, kinase, insulin pathway, wnt signaling pathway, transferase serine/threonine-protein kinase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P49841
• Total number of polymer chains: 1
• Total formula weight: 40299.14

Authors

Dajani, R.,Pearl, L.H.,Roe, S.M. (deposition date: 2004-01-14, release date: 2004-01-29, Last modification date: 2023-12-13)

Primary citation

Meijer, L.,Skaltsounis, A.-L.,Magiatis, P.,Polychronopoulous, P.,Knockaert, M.,Leost, M.,Ryan, X.P.,Vonica, C.A.,Brivanlou, A.,Dajani, R.,Crovace, C.,Tarricone, C.,Musacchio, A.,Roe, S.M.,Pearl, L.H.,Greengard, P.
Gsk-3-Selective Inhibitors Derived from Tyrian Purple Indurubins
Chem.Biol., 10:1255-, 2003

PubMed Abstract: Gastropod mollusks have been used for over 2500 years to produce the "Tyrian purple" dye made famous by the Phoenicians. This dye is constituted of mixed bromine-substituted indigo and indirubin isomers. Among these, the new natural product 6-bromoindirubin and its synthetic, cell-permeable derivative, 6-bromoindirubin-3'-oxime (BIO), display remarkable selective inhibition of glycogen synthase kinase-3 (GSK-3). Cocrystal structure of GSK-3beta/BIO and CDK5/p25/indirubin-3'-oxime were resolved, providing a detailed view of indirubins' interactions within the ATP binding pocket of these kinases. BIO but not 1-methyl-BIO, its kinase inactive analog, also inhibited the phosphorylation on Tyr276/216, a GSK-3alpha/beta activation site. BIO but not 1-methyl-BIO reduced beta-catenin phosphorylation on a GSK-3-specific site in cellular models. BIO but not 1-methyl-BIO closely mimicked Wnt signaling in Xenopus embryos. 6-bromoindirubins thus provide a new scaffold for the development of selective and potent pharmacological inhibitors of GSK-3.

PubMed: 14700633
DOI: 10.1016/J.CHEMBIOL.2003.11.010

Experimental method

X-RAY DIFFRACTION (2.8 Å)