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Catalytically Active MAP KAP Kinase 2 Structures in Complex with Staurosporine and ADP Reveal Differences with the Autoinhibited Enzyme
- Source :
- Structure. 11(6):627-636
- Publication Year :
- 2003
- Publisher :
- Elsevier BV, 2003.
-
Abstract
- 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 Å and with ADP at 3.2 Å, revealing overall structural similarity with other Ser/Thr kinases. Kinetic analysis reveals that the Km 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 Vmax and Km for peptide substrate to values comparable to those seen in p38-activated MK2 41–400, suggesting a mechanism for regulation of enzyme activity.
- Subjects :
- Models, Molecular
Stereochemistry
Macromolecular Substances
p38 mitogen-activated protein kinases
Molecular Sequence Data
Biology
Protein Serine-Threonine Kinases
p38 Mitogen-Activated Protein Kinases
Enzyme activator
Protein structure
Structural Biology
medicine
Staurosporine
Humans
Amino Acid Sequence
Phosphorylation
Peptide sequence
Molecular Biology
chemistry.chemical_classification
Molecular Structure
Kinase
Intracellular Signaling Peptides and Proteins
Protein Structure, Tertiary
Adenosine Diphosphate
Enzyme Activation
Enzyme
chemistry
Mitogen-Activated Protein Kinases
Sequence Alignment
medicine.drug
Subjects
Details
- ISSN :
- 09692126
- Volume :
- 11
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Structure
- Accession number :
- edsair.doi.dedup.....097acf64f2226a080302c56bfbe63f41
- Full Text :
- https://doi.org/10.1016/s0969-2126(03)00092-3