1GZK

Molecular mechanism for the regulation of protein kinase B/Akt by hydrophobic motif phosphorylation

Summary for 1GZK

• Entry DOI: 10.2210/pdb1gzk/pdb
• Related: 1GZN 1GZO 1O6K 1O6L
• Descriptor: RAC-BETA SERINE/THREONINE PROTEIN KINASE (2 entities in total)
• Functional Keywords: kinase, transferase, serine/threonine-protein kinase, atp-binding
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 36490.88

Authors

Barford, D.,Yang, J.,Hemmings, B.A. (deposition date: 2002-05-23, release date: 2003-05-22, Last modification date: 2023-12-13)

Primary citation

Yang, J.,Cron, P.,Thompson, V.,Good, V.,Hess, D.,Hemmings, B.A.,Barford, D.
Molecular Mechanism for the Regulation of Protein Kinase B/Akt by Hydrophobic Motif Phosphorylation
Mol.Cell, 9:1227-, 2002

PubMed Abstract: Protein kinase B/Akt plays crucial roles in promoting cell survival and mediating insulin responses. The enzyme is stimulated by phosphorylation at two regulatory sites: Thr 309 of the activation segment and Ser 474 of the hydrophobic motif, a conserved feature of many AGC kinases. Analysis of the crystal structures of the unphosphorylated and Thr 309 phosphorylated states of the PKB kinase domain provides a molecular explanation for regulation by Ser 474 phosphorylation. Activation by Ser 474 phosphorylation occurs via a disorder to order transition of the alphaC helix with concomitant restructuring of the activation segment and reconfiguration of the kinase bilobal structure. These conformational changes are mediated by a phosphorylation-promoted interaction of the hydrophobic motif with a channel on the N-terminal lobe induced by the ordered alphaC helix and are mimicked by peptides corresponding to the hydrophobic motif of PKB and potently by the hydrophobic motif of PRK2.

PubMed: 12086620
DOI: 10.1016/S1097-2765(02)00550-6

Experimental method

X-RAY DIFFRACTION (2.3 Å)