Crystal structure of an inactive Akt2 kinase domain

Structure. 2003 Jan;11(1):21-30. doi: 10.1016/s0969-2126(02)00937-1.

Abstract

Akt/PKB represents a subfamily of three isoforms from the AGC serine/threonine kinase family. Amplification of Akt activity has been implicated in diseases that involve inappropriate cell survival, including a number of human malignancies. The structure of an inactive and unliganded Akt2 kinase domain reveals several features that distinguish it from other kinases. Most of the alpha helix C is disordered. The activation loop in this structure adopts a conformation that appears to sterically hinder the binding of both ATP and peptide substrate. In addition, an intramolecular disulfide bond is observed between two cysteines in the activation loop. Residues within the linker region between the N- and C-terminal lobes also contribute to the inactive conformation by partially occupying the ATP binding site.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Binding Sites
  • Cyclic AMP-Dependent Protein Kinases / chemistry
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / chemistry*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Sequence Alignment

Substances

  • Ligands
  • Proto-Oncogene Proteins
  • Adenosine Triphosphate
  • AKT1 protein, human
  • AKT2 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Cyclic AMP-Dependent Protein Kinases

Associated data

  • PDB/1MRV
  • PDB/1MRY