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Bejan Hakimi and Brendan Walker 3/4/09

GLYCOGEN SYNTHASE KINASE 3 BETAGLYCOGEN SYNTHASE KINASE 3 BETA

Glycogen Synthase Kinase 3 Beta has in the two opposite quadrants and in the other two opposite quadrants. There are also two active sites that can be seen here:

This view of the protein shows an ampiphilic character in regards to the protein containing a hydrophobic core (black) surrounded by hydrophilic surface residues (green) that stretch farther out from the protein than do the hydrophobic elements. This trend occurs throughout the protein for the most part and can be seen in both the alpha and beta structures and can be seen by rotating the protein. .

spinqualitylabelsall models PDB ID 1h8f Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
1h8f, resolution 2.80Å ()
Ligands:
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.