From Proteopedia

Methionine adenosyltransferase

Methionine adenosyltransferase (MAT) synthesizes S-adenosylmethionine from the substrates adenosine triphosphate (ATP) and methionine. ATP isn’t used as a source of energy like it is in other reactions but gets a methionine added onto the 5th carbon while the three phosphate groups are broken down and released from the active site. This enzyme is conserved and found in many organisms, so it is essential for life. Problems with this enzyme have been shown to cause diseases such as various cancers.

Relevance

Active Site Mechanism

The slightly negative sulfur atom of methionine undergoes a nucleophilic attack on the slightly positive 5th carbon of the adenosine sugar unit. Following this, the bond from the 5th carbon to the oxygen breaks, separating the tripolyphosphate from the newly formed S-adenosylmethionine (SAM) ^[1]. This is an example of an SN2 reaction, where an intermediate forms as the substrates are transitioning to their product forms. The product is only released after the methionine binds and the C-O bond breaks.

Structure

References

1. ↑ ^{1.0 1.1} Murray B, Antonyuk SV, Marina A, Lu SC, Mato JM, Hasnain SS, Rojas Al. Crystallography captures catalytic steps in human methionine adenosyltransferase enzymes. PNAS. 2016 Feb 8;113 (8) 2104-2109. doi: https://doi.org/10.1073/pnas.1510959113
2. ↑ Niland CN, Ghosh A, Cahill SM, Schramm VL. Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. ACS Biochemistry. 2021 Mar 3