Chen P, Luo C, Deng Y, Ryan K, Register J, Margosiak S, Tempczyk-Russell A, Nguyen B, Myers P, Lundgren K, Kan C C, O'Connor P M
Agouron Pharmaceuticals, Inc. San Diego, California 92121, USA.
Cell. 2000 Mar 17;100(6):681-92. doi: 10.1016/s0092-8674(00)80704-7.
The checkpoint kinase Chk1 is an important mediator of cell cycle arrest following DNA damage. The 1.7 A 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.
关卡激酶Chk1是DNA损伤后细胞周期停滞的重要介导因子。人Chk1激酶结构域及其与ATP类似物的二元复合物的1.7埃分辨率晶体结构显示出相同的开放激酶构象。二级结构和侧链相互作用稳定了Chk1的激活环，并在催化结构域未磷酸化的情况下实现激酶活性。Cdc25C肽与Chk1相互作用的分子建模揭示了几个对底物选择性很重要的保守残基。此外，我们发现保守性较低的C末端区域对Chk1激酶活性有负面影响。
