Diabetes is the world's most common metabolic disorder. By 2025, the number of adults with diabetes is expected to reach 300 million worldwide. The disease, which is associated with obesity and inactivity, is the sixth leading cause of death in the United States, killing nearly 200,000 people every year.
In diabetes, there is too much glucose in the blood. People with type I diabetes cannot produce enough insulin to trigger the conversion of food to energy. Insulin works by stimulating the uptake of glucose into cells and by suppressing the production of glucose by the liver. People with the more common type 2 diabetes produce enough insulin but the cells that normally respond to insulin fail to do so.
To develop new therapies for diabetes it is important to identify and understand how the many components of the insulin-signaling pathway work. This pathway includes protein kinases and phosphatases. Protein kinases transfer phosphate from the high-energy molecule ATP to a particular amino acid on target proteins, thus regulating the activity of these proteins. The pathway is switched off by phosphatases that remove phosphate from proteins. Protein kinases and phosphatases are both potential targets for therapeutic intervention.
One possible drug target is the protein kinase GSK3beta. It is known to regulate blood glucose levels and becomes less active when cells are stimulated with insulin. Now, in the July issue of Nature Structural Biology (Vol. 8, No. 7), ter Haar and coworkers of Vertex Pharmaceuticals Inc. in Cambridge, Massachusetts, USA, have solved the three-dimensional crystal structure of the protein. The structure explains a unique property of this enzyme, namely, that it prefers to add phosphates to proteins that have already been phosphorylated. This finding may help in the design of specific inhibitors of this enzyme.
Dr. Ernst ter Haar
Vertex Pharmaceuticals Incorporated
130 Waverly Street
Cambridge, Massachusetts 02139-4211
Telephone: 617 577 6243
Fax: 617 577 6400
(C) Nature Structural Biology press release.
Message posted by: Trevor M. D'Souza