A highly diverged ancient interface plays a key role in the origin and evolution of Methionine AdenosylTransferase superfamily

Abstract

Methionine adenosyltransferase (MAT), which catalyzes the biosynthesis of S-adenosylmethionine from L-methionine and ATP, is an ancient, highly conserved enzyme present in all three domains of life. Although the MAT enzymes of each domain are believed to share a common ancestor, the sequences of archaeal MATs show a high degree of divergence from the sequences of bacterial and eukaryotic MATs. However, the structural and functional consequences of this sequence divergence are not well understood. Here, we use structural bioinformatics analysis and ancestral sequence reconstruction to highlight the consequences of archaeal MAT divergence. We show that the dimer interface containing the active site, which would be expected to be well conserved across all three domains, diverged considerably between the bacterial/eukaryotic MATs and archaeal MATs. Furthermore, the characterization of reconstructed ancestral archaeal MATs showed that they probably had low substrate specificity which expanded during their evolutionary trajectory hinting towards the observation that all the modern day MAT enzymes from the three-kingdom probably originated from a common specific ancestor and then archaea MATs diverged in sequence, structure and substrate specificity. Altogether, our results show that the archaea MAT is an ideal system for studying an enzyme family which evolved to display high degrees of divergence at the sequence/structural levels and yet are capable of performing the same catalytic reactions as their orthologous counterparts.