Structural insight into substrate specificity and regulatory mechanisms of phosphoinositide 3-kinases

Trends Biochem Sci. 2002 Aug;27(8):426-32. doi: 10.1016/s0968-0004(02)02136-9.

Abstract

Phosphoinositide 3-kinases (PI3Ks) are implicated in a variety of fundamental cellular processes. These enzymes catalyse phosphorylation of the 3'-OH position of myo-inositol lipids that serve as secondary messengers. The catalytic subunit for one of the family members, PI3K gamma, has been structurally characterized, independently, in complexes with kinase inhibitors and with the p21(Ras) GTPase. These atomic structures provide a basis for the rationalization of some PI3K substrate specificities and regulatory mechanisms, establishing links to functional and cellular data. Ongoing comprehensive structural and functional studies are essential to realize the promise of PI3K isozyme-specific therapeutic agents.

Publication types

  • Review

MeSH terms

  • Binding Sites
  • Catalytic Domain
  • Chromones / chemistry
  • Chromones / metabolism
  • Chromones / pharmacology
  • Drug Design
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Morpholines / chemistry
  • Morpholines / metabolism
  • Morpholines / pharmacology
  • Phosphatidylinositol 3-Kinases / chemistry*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Conformation
  • Protein Folding
  • Protein Kinases / metabolism
  • Substrate Specificity
  • ras Proteins / metabolism

Substances

  • Chromones
  • Enzyme Inhibitors
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Protein Kinases
  • ras Proteins