In silico analysis of the tRNA:m1A58 methyltransferase family: homology-based fold prediction and identification of new members from Eubacteria and Archaea

Abstract

The amino acid sequences of Gcd10p and Gcd14p, the two subunits of the tRNA:(1-methyladenosine-58; m 1A58) methyltransferase (MTase) of Saccharomyces cerevisiae, have been analyzed using iterative sequence database searches and fold recognition programs. The results suggest that the ‘catalytic’ Gcd14p and ‘substrate binding’ Gcd10p are related to each other and to a group of prokaryotic open reading frames, which were previously annotated as hypothetical protein isoaspartate MTases in sequence databases. It is predicted that the prokaryotic proteins are genuine tRNA:m 1A MTases based on similarity of their predicted active site to the Gcd14p family. In addition to the MTase domain, an additional domain was identified in the N-terminus of all these proteins that may be involved in interaction with tRNA. These results suggest that the eukaryotic tRNA:m 1A58 MTase is a product of gene duplication and divergent evolution of a possibly homodimeric prokaryotic enzyme.