Sandbox Reserved 433: Difference between revisions

Glycogen Synthase Kinase-3 (GSK-3) is a serine/threonine kinase monomer and has an overall structure that is characteristic of the apoenzyme. It has two phosphorylation sites that are involved in catalysis. One of these sites is Ser9, which is the phosphorylation site for AKT, resulting in the inactivation of GSK-3beta. The second phosphorylation site is Tyr216, located on the activation loop (shown in green), and is responsible for the increase in catalytic activity. GSK-3beta has the characteristic two-domain kinase fold, containing a N-terminal beta-strand domain (light blue, residues 25-138) and a C-terminal alpha-helical domain (red, residues 139-343). There is an interface between the alpha and beta domains, at which the ATP-binding site is located, encircled by the hinge and the glycine-rich loop.  The activation loop (purple) runs along the surface of the substrate-binding groove. There are 39 residues in the C-terminus end that are outside the main kinase fold.  These residues form a small domain that closely packs next to the alpha-helical domain.  The beta-strand domain is formed by seven beta-strands that run in an antiparallel formation. Strands 2-6 form a beta-barrel, through which a short alpha helix (yellow, residues 96-102) aligns against the beta-barrel. Two of this short helix’s residues play important roles in the catalytic action of GSK-3beta. A salt bridge, which is important in binding interactions, is positioned in the active site between Glu97 and Lys85<ref>PMID: 11427888</ref>.