Crystal Structure and Mutational Analysis of the Human CDK2 Kinase Complex with Cell Cycle–Regulatory Protein CksHs1
| Autor: | Mark H. Watson, Michael J. Hickey, Yves Bourne, William D. Holmes, John A. Tainer, Warren J. Rocque, Steven I. Reed |
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| Rok vydání: | 1996 |
| Předmět: |
Protein Conformation
DNA Mutational Analysis Molecular Sequence Data Cell Cycle Proteins Saccharomyces cerevisiae Protein Serine-Threonine Kinases Sensitivity and Specificity General Biochemistry Genetics and Molecular Biology Cyclin-dependent kinase CDC2-CDC28 Kinases Image Processing Computer-Assisted Humans Transferase Conserved Sequence Cyclin Cyclin-dependent kinase 1 Crystallography Base Sequence Sequence Homology Amino Acid biology Biochemistry Genetics and Molecular Biology(all) Kinase Cell Cycle Cyclin-Dependent Kinase 2 Cyclin-dependent kinase 2 Cell cycle Cyclin-Dependent Kinases Cell biology Biochemistry biology.protein Cyclin-dependent kinase complex Carrier Proteins Protein Kinases Protein Binding |
| Zdroj: | Cell. 84:863-874 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/s0092-8674(00)81065-x |
| Popis: | The 2.6 Angstrom crystal structure for human cyclin-dependent kinase 2(CDK2) in complex with CksHs1, a human homolog of essential yeast cell cycle-regulatory proteins suc1 and Cks1, reveals that CksHs1 binds via all four beta strands to the kinase C-terminal lobe. This interface is biologically critical, based upon mutational analysis, but far from the CDK2 N-terminal lobe, cyclin, and regulatory phosphorylation sites. CDK2 binds the Cks single domain conformation and interacts with conserved hydrophobic residues plus His-60 and Glu-63 in their closed beta-hinge motif conformation. The beta hinge opening to form the Cks beta-interchanged dimer sterically precludes CDK2 binding, providing a possible mechanism regulating CDK2-Cks interactions. One face of the complex exposes the sequence-conserved phosphate-binding region on Cks and the ATP-binding site on CDK2, suggesting that CKs may target CDK2 to other phosphoproteins during the cell cycle. |
| Databáze: | OpenAIRE |
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