1H8F

Glycogen Synthase Kinase 3 beta.

Summary for 1H8F

• Entry DOI: 10.2210/pdb1h8f/pdb
• Descriptor: GLYCOGEN SYNTHASE KINASE-3 BETA, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID (3 entities in total)
• Functional Keywords: kinase, insulin pathway
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 2
• Total formula weight: 80076.10

Authors

Dajani, R.,Pearl, L.H.,Roe, S.M. (deposition date: 2001-02-05, release date: 2002-01-31, Last modification date: 2023-12-13)

Primary citation

Dajani, R.,Fraser, E.,Roe, S.M.,Young, N.,Good, V.,Dale, T.C.,Pearl, L.H.
Crystal Structure of Glycogen Synthase Kinase 3Beta . Structural Basis for Phosphate-Primed Substrate Specificity and Autoinhibition
Cell(Cambridge,Mass.), 105:721-, 2001

PubMed Abstract: 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.

PubMed: 11440715
DOI: 10.1016/S0092-8674(01)00374-9

Experimental method

X-RAY DIFFRACTION (2.8 Å)