Implications for Chk1 Regulation: The 1.7 Å Crystal Structure of Human Cell Cycle Checkpoint Kinase Chk1
| Autor: | Yali Deng, Patrick M O'Connor, Chen-Chen Kan, Pamela Myers, James Register, Luo Chun, Stephen Margosiak, Binh Nguyen, Kevin Ryan, Ping Chen, Karen Lundgren, Anna Tempczyk-Russell |
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| Rok vydání: | 2000 |
| Předmět: |
Cyclin-dependent kinase 1
animal structures Biochemistry Genetics and Molecular Biology(all) genetic processes Cyclin-dependent kinase 2 Cyclin-dependent kinase 3 Biology environment and public health General Biochemistry Genetics and Molecular Biology MAP2K7 Cell biology enzymes and coenzymes (carbohydrates) Cyclin-dependent kinase complex biology.protein biological phenomena cell phenomena and immunity Kinase activity Casein kinase 2 Cyclin-dependent kinase 7 |
| Zdroj: | Cell. 100(6):681-692 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/s0092-8674(00)80704-7 |
| Popis: | The checkpoint kinase Chk1 is an important mediator of cell cycle arrest following DNA damage. The 1.7 Å resolution crystal structures of the human Chk1 kinase domain and its binary complex with an ATP analog has revealed an identical open kinase conformation. The secondary structure and side chain interactions stabilize the activation loop of Chk1 and enable kinase activity without phosphorylation of the catalytic domain. Molecular modeling of the interaction of a Cdc25C peptide with Chk1 has uncovered several conserved residues that are important for substrate selectivity. In addition, we found that the less conserved C-terminal region negatively impacts Chk1 kinase activity. |
| Databáze: | OpenAIRE |
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