A new look at a protein that is often mutated in tumors of the pituitary gland, helps develop a targeted therapy for cancer.
«G-protein" called G? S-, initiates messages within cells. But one mutation can suddenly change operation Gαs. As the researchers reported April 5, 2018 in the journal Cell, a molecular "switch" protein actually switches its activity.
According to study co-author Kevan Shawkat from the University of California in San Francisco, this data will enable scientists to develop new anti-cancer drugs that specifically target the G? S-.
Scientists have discovered an unexpected method of transmitting signals protein G. Protein G include various messaging network. But these proteins may mutate into cancer cells, disrupting biochemical workflow. Anticancer drugs that bind to these mutating proteins may restore normal cell function.
In 2013, researchers have developed a drug to a mutated G protein called K-Ras, which is commonly found in cancer cells, lung and colon. This protein has been targeted by cancer drugs for 30 years. Like all G-proteins, K-Ras includes various messaging network when it captures the high-energy molecule. Shaukat and his colleagues found that the mutation K-Ras, which they have studied, modified protein, causing it to permanently activate the message.
The researchers used the knowledge about the structure and functions of the K-Ras to develop a drug that prevents the survival of the mutated protein.
Since Gαs and K-Ras are part of the same protein family and have similar mutations, Shaukat and his colleagues believed that the change Gαs will have an effect similar to what they observed in the K-Ras. However, scientists realized that he had other functions than those of K-Ras.
The research team had an X-ray crystal structure of the mutated protein Gαs and compare it with the known structures of the active and inactive G-proteins. The structure of the mutated Gαs was more like a sibling active G-protein than inactive. The result of this was that the mutated Gαs remained active. This suggests that the proteins have a number of ways to stay active and medicine will deactivate the proteins in the cancer cells.