InterPro domain: IPR003358

This entry represents tRNA (guanine-N-7) methyltransferase ( 2.1.1.33 ), which catalyses the formation of N(7)-methylguanine at position 46 (m7G46) in tRNA. Capping of the pre-mRNA 5' end by addition a monomethylated guanosine cap (m(7)G) is an essential and the earliest modification in the biogenesis of mRNA [ 1 ]. The reaction is catalysed by three enzymes: triphosphatase, guanylyltransferase, and tRNA (guanine-N-7) methyltransferase [ 2 , 3 ]. This entry includes Bacillus subtilis TrmB, which contains a unique variant of the Rossmann-fold methyltransferase (RFM) structure, with the N-terminal helix folded on the opposite site of the catalytic domain [ 4 ].

Methyltransferases (EC [intenz:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule [ 5 , 6 , 7 ]. All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM [ 8 ]. The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids [ 9 , 9 , 9 ]. Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing [ 9 , 9 , 9 ]. More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.

1. Evidence for a capping enzyme with specificity for the trypanosome spliced leader RNA. Mol. Biochem. Parasitol. 156, 246-54
2. Two proteins that form a complex are required for 7-methylguanosine modification of yeast tRNA. RNA 8, 1253-66
3. Crystal structure of the methyltransferase domain of human TARBP1. Proteins 72, 519-25
4. Crystal structure of Bacillus subtilis TrmB, the tRNA (m7G46) methyltransferase. Nucleic Acids Res. 34, 1925-34
5. Natural history of S-adenosylmethionine-binding proteins. BMC Struct. Biol. 5, 19
6. Comprehensive structural and substrate specificity classification of the Saccharomyces cerevisiae methyltransferome. PLoS ONE 6, e23168
7. Many paths to methyltransfer: a chronicle of convergence. Trends Biochem. Sci. 28, 329-35
8. Universal catalytic domain structure of AdoMet-dependent methyltransferases. J. Mol. Biol. 247, 16-20