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Bejan Hakimi and Brendan Walker 3/4/09

GLYCOGEN SYNTHASE KINASE 3 BETA

Glycogen Synthase Kinase 3 Beta has beta sheet in the two opposite quadrants and alpha helices in the other two opposite quadrants. There are also two active sites that can be seen here: Active Sites This view shows a hydrophobic element of an alpha helix (in red) on the surface of the protein.

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1h8f, resolution 2.80Å (default scene)
Ligands:	EPE
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Structural annotation: Resources: CATH : 1H8Fa02, 1H8Fa01, 1H8Fb02, 1H8Fb01 InterPro : Ipr011009, Ipr000719, Ipr008271, Ipr002290 Pfam : PF00069 SCOP : d1h8fa_, d1h8fb_ UniProt : P49841
Functional annotation: Cellular component: cytoplasm nucleus beta-catenin destruction complex Biological process: positive regulation of protein export from nucleus peptidyl-serine phosphorylation Wnt receptor signaling pathway through beta-catenin ER overload response Wnt receptor signaling pathway negative regulation of apoptosis protein amino acid phosphorylation intracellular signaling cascade glycogen metabolic process Molecular function: nucleotide binding ATP binding transferase activity p53 binding NF-kappaB binding kinase activity protein serine/threonine kinase activity protein kinase activity protein binding glycogen synthase kinase 3 activity
Evolutionary conservation: Toggle Conservation Colors: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, RCSB, PDBsum
Coordinates:	save as pdb, mmCIF, xml

Publication Abstract from PubMed

Glycogen synthase kinase 3 beta (GSK3 beta) plays a key role in insulin and Wnt signaling, phosphorylating downstream targets by default, and becoming inhibited following the extracellular signaling event. The crystal structure of human GSK3 beta shows a catalytically active conformation in the absence of activation-segment phosphorylation, with the sulphonate of a buffer molecule bridging the activation-segment and N-terminal domain in the same way as the phosphate group of the activation-segment phospho-Ser/Thr in other kinases. The location of this oxyanion binding site in the substrate binding cleft indicates direct coupling of P+4 phosphate-primed substrate binding and catalytic activation, explains the ability of GSK3 beta to processively hyperphosphorylate substrates with Ser/Thr pentad-repeats, and suggests a mechanism for autoinhibition in which the phosphorylated N terminus binds as a competitive pseudosubstrate with phospho-Ser 9 occupying the P+4 site.

Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition., Dajani R, Fraser E, Roe SM, Young N, Good V, Dale TC, Pearl LH, Cell. 2001 Jun 15;105(6):721-32. PMID:11440715

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.