An international team of scientists led by the University of
Liverpool has produced a 'structural movie' revealing 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. Methylation is an underpinning process of life and provides
control for biological processes such as DNA synthesis, cell growth and
apoptosis.
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.
The international team, which includes researchers from the Center
for Cooperative Research in Biosciences, Spain, and Cedars-Sinai Medical
Center, Los Angeles, used X-ray crystallography to successfully unravel
how the catalytic subunit MATĪ±2 synthesises SAMe, with details of every
atom's location and behaviour as the synthesis takes place.
The work was led by Professor Samar Hasnain and Dr Svetlana Antonyuk
who are co-directors of the University's Barkla X-ray Laboratory of
Biophysics and utilised some of Europe's most powerful X-ray synchrotron
sources, including ALBA in Spain and DIAMOND in the UK."Though the relationship between SAMe and tumour 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.
"The good news is that MATĪ±2 is only over-expressed 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."
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