Scientists at Vanderbilt University and Northwestern University have determined the three-dimensional structure of a critical region of Death Associated Protein Kinase (DAPK) and created a quantitative assay capable of measuring its activity.
These results were published in the October issue of Nature Structural Biology and the October 19 issue of the Journal of Biological Chemistry and are generating considerable interest in the pharmaceutical industry because DAPK provides a new target for the development of drugs that could reduce cell damage following brain injuries and stroke.
The senior authors of the two papers are Martin Egli, associate professor of biological sciences at Vanderbilt University, and D. Martin Watterson, director of the Drug Discovery Program at Northwestern University. Eglis group mapped the three-dimensional structure of DAPKs kinase domain and Wattersons group developed the quantitative assay. DAPK is a large protein with a number of distinct domains. It was discovered in 1995 by Adi Kimchi at the Weizmann Institute of Science in Israel while screening the entire genome for genes that promote a process called programmed cell death and inhibit tumor growth.
DAPK contains a "death domain" that can initiate a cascade of molecular events that cause a cell to commit suicide. This process, called programmed cell death or apoptosis, is programmed into all but the most primitive of cells. It causes the cell to shut down in an orderly manner so that its contents can be absorbed by surrounding cells without initiating an attack by the bodys internal self-defense systems. This is particularly important in enclosed areas like the brain.
Previous research has implicated DAPK in a wide range of apoptotic systems an
Contact: David F. Salisbury