Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex

Nature. 1995 Jul 27;376(6538):313-20. doi: 10.1038/376313a0.

Abstract

The crystal structure of the human cyclinA-cyclin-dependent kinase2 (CDK2)-ATP complex has been determined at 2.3 A resolution. CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / metabolism
  • Allosteric Regulation
  • Amino Acid Sequence
  • Binding Sites
  • CDC2-CDC28 Kinases*
  • Computer Graphics
  • Crystallography, X-Ray
  • Cyclic AMP-Dependent Protein Kinases / chemistry
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases / chemistry*
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / chemistry*
  • Cyclins / metabolism
  • Enzyme Activation
  • Escherichia coli
  • Humans
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Binding
  • Protein Conformation
  • Protein Folding
  • Protein Serine-Threonine Kinases / chemistry*
  • Protein Serine-Threonine Kinases / metabolism
  • Recombinant Proteins / chemistry
  • Threonine / chemistry

Substances

  • Cyclins
  • Recombinant Proteins
  • Threonine
  • Adenosine Triphosphate
  • Protein Serine-Threonine Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases