Research reported in the Journal of Biological Chemistry found a new binding site for Mps1 kinase.
A team of investigators from University of Manchester uncovered the structure of Mps1, a kinase regulator of chromosomal stability and a potential target in cancer therapy. The protein prevents aneuploidy, the change in the number of chromosomes, which is closely associated with cancer.
The researchers used the Diamond Light synchrotron, and the resulting X-rays were fired at a pure sample of Mps1.This allowed them to see the protein’s atomic structure. This revealed the pocket where Mps1 binds to ATP.
Further work showed the protein in complex with the ATP-competitive inhibitor SP600125, a well-known but nonspecific inhibitor of many kinases, which revealed a secondary pocket not utilized by this compound, the scientists report. They suggest that if a drug can be designed to specifically block this secondary pocket, Mps1 may be specifically disabled, killing rapidly dividing cells such as those found in tumors.
The findings are published in the August issue of the Journal of Biological Chemistry.
