Researchers at the University of Liverpool have described the step-by-step creation of an important naturally occurring chemical in the body that plays a role in some cancers. S-Adenosylmethionine (SAMe) is a major methyl donor that is produced by the highly conserved Methionine Adenosyltransferase (MAT) family of enzymes.
Tight regulation of the level of SAMe is essential for maintaining a healthy cell, and dysregulation of SAMe is considered important in many diseases including liver and colon cancer.
An international team, which includes researchers from the Center for Cooperative Research in Biosciences, Spain, and Cedars-Sinai Medical Center in Los Angeles, used X-ray crystallography to unravel how the catalytic subunit MATα2 synthesizes SAMe, with details of every atom's location and behavior as the synthesis takes place.
The work was led by Samar Hasnain, Ph.D., and Svetlana Antonyuk, Ph.D., who are co-directors of the University's Barkla X-ray Laboratory of Biophysics and used some of Europe's most powerful X-ray synchrotron sources, including ALBA in Spain and DIAMOND in the U.K.
According to Dr. Antonyuk, “Our work has provided a detailed insight into the synthesis of SAMe by this human enzyme and has opened the way to target it for therapeutic purposes for hepatocellular carcinoma and colon cancer.”
“Though the relationship between SAMe and tumor growth has been known for some time, this molecule also has other important functions inside the cell that cannot be altered, and there is currently no way of acting against it without affecting these other life-sustaining functions,” said Dr. Hasnain. “The good news is that MATα2 is only overexpressed in adults with tumors, therefore representing an excellent therapeutic target, which could open the door to the creation of highly targeted drugs that act exclusively on this enzyme rather than attacking other regions of the body.”
The scientists' study (“Crystallography captures catalytic steps in human methionine adenosyltransferase enzymes”) is published in Proceedings of the National Academy of Sciences.