Structural basis of cyclin-dependent kinase activation by phosphorylation

Nat Struct Biol. 1996 Aug;3(8):696-700. doi: 10.1038/nsb0896-696.

Abstract

Cyclin-dependent kinase (CDK)-cyclin complexes require phosphorylation on the CDK subunit for full activation of their Ser/Thr protein kinase activity. The crystal structure of the phosphorylated CDK2-CyclinA-ATP gamma S complex has been determined at 2.6 A resolution. The phosphate group, which is on the regulatory T-loop of CDK2, is mostly buried, its charge being neutralized by three Arg side chains. The arginines help extend the influence of the phosphate group through a network of hydrogen bonds to both CDK2 and cyclinA. Comparison with the unphosphorylated CDK2-CyclinA complex shows that the T-loop moves by as much as 7 A, and this affects the putative substrate binding site as well as resulting in additional CDK2-CyclinA contacts. The phosphate group thus acts as a major organizing centre in the CDK2-CyclinA complex.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives*
  • Adenosine Triphosphate / chemistry
  • CDC2-CDC28 Kinases*
  • Conserved Sequence
  • Crystallography
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases / chemistry*
  • Cyclins / chemistry*
  • Enzyme Activation
  • Models, Molecular
  • Phosphoproteins / chemistry*
  • Phosphorylation
  • Protein Conformation
  • Protein-Serine-Threonine Kinases / chemistry*

Substances

  • Cyclins
  • Phosphoproteins
  • adenosine 5'-O-(3-thiotriphosphate)
  • Adenosine Triphosphate
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases