The 1.7 angstrom crystal structure of human cell cycle checkpoint kinase Chk1: Implications for Chk1 regulation

The checkpoint kinase Chk1 is an important mediator of cell cycle arrest fo llowing DNA damage. The 1.7 Angstrom resolution crystal structures of the h uman Chk1 kinase domain and its binary complex with an ATP analog has revea led 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 modeli ng of the interaction of a Cdc25C peptide with Chk1 has uncovered several c onserved residues that are important for substrate selectivity. In addition , we found that the less conserved C-terminal region negatively impacts Chk 1 kinase activity.