Crystal structure of the catalytic core of inositol 1,4,5-trisphosphate 3-kinase

Mol Cell. 2004 Sep 10;15(5):703-11. doi: 10.1016/j.molcel.2004.08.005.


Soluble inositol polyphosphates are ubiquitous second messengers in eukaryotes, and their levels are regulated by an array of specialized kinases. The structure of an archetypal member of this class, inositol 1,4,5-trisphosphate 3-kinase (IP3K), has been determined at 2.2 angstroms resolution in complex with magnesium and adenosine diphosphate. IP3K contains a catalytic domain that is a variant of the protein kinase superfamily, and a novel four-helix substrate binding domain. The two domains are in an open conformation with respect to each other, suggesting that substrate recognition and catalysis by IP3K involves a dynamic conformational cycle. The unique helical domain of IP3K blocks access to the active site by membrane-bound phosphoinositides, explaining the structural basis for soluble inositol polyphosphate specificity.

MeSH terms

  • Adenosine Diphosphate / chemistry
  • Amino Acid Sequence
  • Animals
  • Binding Sites / physiology
  • Catalytic Domain / physiology*
  • Cell Membrane / chemistry
  • Crystallography, X-Ray
  • Magnesium / chemistry
  • Models, Molecular
  • Molecular Conformation
  • Molecular Sequence Data
  • Molecular Structure
  • Phosphatidylinositols / metabolism
  • Phosphotransferases (Alcohol Group Acceptor) / chemistry*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Protein Binding / physiology*
  • Rats
  • Sequence Homology, Amino Acid


  • Phosphatidylinositols
  • Adenosine Diphosphate
  • Phosphotransferases (Alcohol Group Acceptor)
  • Inositol 1,4,5-trisphosphate 3-kinase
  • Magnesium

Associated data

  • PDB/1TZD