The 1.7 Å crystal structure of human cell cycle checkpoint kinase Chk1:: Implications for Chk1 regulation
The 1.7 Å crystal structure of human cell cycle checkpoint kinase Chk1:: Implications for Chk1 regulation
复制标题
DOI：
10.1016/s0092-8674(00)80704-7
复制
发表时间：
2000-03-17
期刊：
影响因子：
64.5
通讯作者：
O'Connor, PM
中科院分区：
文献类型：
--
作者：
Chen, P;Luo, C;O'Connor, PM
检查点激酶Chk 1是DNA损伤后细胞周期阻滞的重要介质。人Chk 1激酶结构域及其与ATP类似物的二元复合物的1.7埃分辨率晶体结构揭示了相同的开放激酶构象。二级结构和侧链相互作用稳定了Chk 1的激活环，并在催化结构域不磷酸化的情况下实现了激酶活性。Cdc 25 C肽与Chk 1相互作用的分子建模已经发现了几个保守的残基，这些残基对底物选择性很重要。此外，我们发现，保守性较低的C-末端区域的Chk 1激酶活性产生负面影响。
The checkpoint kinase Chk1 is an important mediator of cell cycle arrest following DNA damage. The 1.7 Angstrom 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.