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 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
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Adenosine Diphosphate / metabolism*
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Amino Acid Sequence
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Enzyme Activation
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Humans
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Intracellular Signaling Peptides and Proteins
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Macromolecular Substances
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Mitogen-Activated Protein Kinases / metabolism
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Models, Molecular
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Molecular Sequence Data
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Molecular Structure
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Phosphorylation
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Protein Serine-Threonine Kinases / chemistry*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Protein Structure, Tertiary*
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Sequence Alignment
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Staurosporine / metabolism*
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p38 Mitogen-Activated Protein Kinases
Substances
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Intracellular Signaling Peptides and Proteins
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Macromolecular Substances
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Adenosine Diphosphate
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MAP-kinase-activated kinase 2
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Protein Serine-Threonine Kinases
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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Staurosporine