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

The amino acid sequences of Gcd10p and Gcd14p, the two subunits of the (RNA : (1-methyladenosine-58; m(1)A58) methyltransferase (MTase) of Saccharomyce s cerevisiae, have been analyzed using iterative sequence database searches and fold recognition programs. The results suggest that the 'catalytic' Ge d14p and 'substrate binding' Gcd10p are related to each other and to a grou p of prokaryotic open reading frames, which were previously annotated as hy pothetical protein isoaspartate MTases in sequence databases. It is predict ed that the prokaryotic proteins are genuine tRNA:m(1)A MTases based on sim ilarity 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 re sults suggest that the eukaryotic tRNA:m(1) A58 MTase is a product of gene duplication and divergent evolution of a possibly homodimeric prokaryotic e nzyme. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.