Catalytically active MAP KAP kinase 2 structures in complex with staurosporine and ADP reveal differences with the autoinhibited enzyme

Structure. 2003 Jun;11(6):627-36. doi: 10.1016/s0969-2126(03)00092-3.


MAP KAP kinase 2 (MK2), a Ser/Thr kinase, plays a crucial role in the inflammatory process. We have determined the crystal structures of a catalytically active C-terminal deletion form of human MK2, residues 41-364, in complex with staurosporine at 2.7 A and with ADP at 3.2 A, revealing overall structural similarity with other Ser/Thr kinases. Kinetic analysis reveals that the K(m) for ATP is very similar for MK2 41-364 and p38-activated MK2 41-400. Conversely, the catalytic rate and binding for peptide substrate are dramatically reduced in MK2 41-364. However, phosphorylation of MK2 41-364 by p38 restores the V(max) and K(m) for peptide substrate to values comparable to those seen in p38-activated MK2 41-400, suggesting a mechanism for regulation of enzyme activity.

MeSH terms

  • Adenosine Diphosphate / metabolism*
  • Amino Acid Sequence
  • Enzyme Activation
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Macromolecular Substances
  • Mitogen-Activated Protein Kinases / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Phosphorylation
  • Protein Serine-Threonine Kinases / chemistry*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Structure, Tertiary*
  • Sequence Alignment
  • Staurosporine / metabolism*
  • p38 Mitogen-Activated Protein Kinases


  • Intracellular Signaling Peptides and Proteins
  • Macromolecular Substances
  • Adenosine Diphosphate
  • MAP-kinase-activated kinase 2
  • Protein Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Staurosporine

Associated data

  • PDB/1NXK
  • PDB/1NY3