Abstract
The crystal structure of the human p27Kip1 kinase inhibitory domain bound to the phosphorylated cyclin A-cyclin-dependent kinase 2 (Cdk2) complex has been determined at 2.3 angstrom. p27Kip1 binds the complex as an extended structure interacting with both cyclin A and Cdk2. On cyclin A, it binds in a groove formed by conserved cyclin box residues. On Cdk2, it binds and rearranges the amino-terminal lobe and also inserts into the catalytic cleft, mimicking ATP.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Binding Sites
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CDC2-CDC28 Kinases*
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Cell Cycle Proteins*
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Conserved Sequence
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Crystallography, X-Ray
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclin-Dependent Kinases / antagonists & inhibitors
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Cyclin-Dependent Kinases / chemistry*
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Cyclin-Dependent Kinases / metabolism
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Cyclins / chemistry*
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Cyclins / metabolism
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / metabolism
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Humans
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Microtubule-Associated Proteins / chemistry*
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Microtubule-Associated Proteins / metabolism
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Molecular Sequence Data
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Protein Binding
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / chemistry*
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Protein Serine-Threonine Kinases / metabolism
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Tumor Suppressor Proteins*
Substances
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Cell Cycle Proteins
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Cyclins
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Enzyme Inhibitors
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Microtubule-Associated Proteins
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Tumor Suppressor Proteins
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Cyclin-Dependent Kinase Inhibitor p27
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Protein Serine-Threonine Kinases
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CDC2-CDC28 Kinases
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CDK2 protein, human
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases