CATALYTIC DOMAIN OF THE HUMAN EFFECTOR CELL CYCLE CHECKPOINTPROTEIN KINASE, CHK1, MATERIALS AND METHODS FOR IDENTIFICATION OF INHIBITORS THEREOF

摘要

The present invention relates to the identification, isolation and purification of the catalytic domain of the human effector checkpoint protein kinase (hChkl). A 1.7O crystal structure of the hChkl kinase domain in the active conformation is reported herein. The kinase domain of hChkl and its associated crystal structure is described for use in the discovery, identification and characterization of inhibitors of hChkl. This structure provides a three-dimensional description of the binding site of the hChkl for structure - based design of small molecule inhibitors thereof as therapeutic agents. Inhibitors of hChkl find utility in the treatment of hyperproliferative disorders such as HIV and cancer.