1gzk: Difference between revisions
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'''MOLECULAR MECHANISM FOR THE REGULATION OF PROTEIN KINASE B/ AKT BY HYDROPHOBIC MOTIF PHOSPHORYLATION''' | '''MOLECULAR MECHANISM FOR THE REGULATION OF PROTEIN KINASE B/ AKT BY HYDROPHOBIC MOTIF PHOSPHORYLATION''' | ||
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[[Category: Hemmings, B A.]] | [[Category: Hemmings, B A.]] | ||
[[Category: Yang, J.]] | [[Category: Yang, J.]] | ||
[[Category: | [[Category: Atp-binding]] | ||
[[Category: | [[Category: Serine/threonine-protein kinase]] | ||
[[Category: | [[Category: Transferase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:13:19 2008'' | |||
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Revision as of 18:13, 2 May 2008
MOLECULAR MECHANISM FOR THE REGULATION OF PROTEIN KINASE B/ AKT BY HYDROPHOBIC MOTIF PHOSPHORYLATION
OverviewOverview
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.
About this StructureAbout this Structure
1GZK is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Molecular mechanism for the regulation of protein kinase B/Akt by hydrophobic motif phosphorylation., Yang J, Cron P, Thompson V, Good VM, Hess D, Hemmings BA, Barford D, Mol Cell. 2002 Jun;9(6):1227-40. PMID:12086620 Page seeded by OCA on Fri May 2 18:13:19 2008