SNAP output for PDB entry 4n48 [SNAP web server]

PDB-id

4n48; SNAP-derived features in text and JSON formats; DNAproDB

Class

transferase-RNA

Method

X-ray (2.704 Å)

Summary

Cap-specific mrna (nucleoside-2'-o-)-methyltransferase 1 protein in complex with capped RNA fragment

Reference

Smietanski M, Werner M, Purta E, Kaminska KH, Stepinski J, Darzynkiewicz E, Nowotny M, Bujnicki JM (2014): "Structural analysis of human 2'-O-ribose methyltransferases involved in mRNA cap structure formation." Nat Commun, 5, 3004. doi: 10.1038/ncomms4004.

Abstract

The 5' cap of human messenger RNA contains 2'-O-methylation of the first and often second transcribed nucleotide that is important for its processing, translation and stability. Human enzymes that methylate these nucleotides, termed CMTr1 and CMTr2, respectively, have recently been identified. However, the structures of these enzymes and their mechanisms of action remain unknown. In the present study, we solve the crystal structures of the active CMTr1 catalytic domain in complex with a methyl group donor and a capped oligoribonucleotide, thereby revealing the mechanism of specific recognition of capped RNA. This mechanism differs significantly from viral enzymes, thus providing a framework for their specific targeting. Based on the crystal structure of CMTr1, a comparative model of the CMTr2 catalytic domain is generated. This model, together with mutational analysis, leads to the identification of residues involved in RNA and methyl group donor binding.