4N4A

Cystal structure of Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase 1

Summary for 4N4A

• Entry DOI: 10.2210/pdb4n4a/pdb
• Related: 4N48 4N49
• Descriptor: Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase 1 (2 entities in total)
• Functional Keywords: methyltransferase, mrna cap methylation, mrna, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : Q8N1G2
• Total number of polymer chains: 1
• Total formula weight: 48935.75

Authors

Smietanski, M.,Werener, M.,Purta, E.,Kaminska, K.H.,Stepinski, J.,Darzynkiewicz, E.,Nowotny, M.,Bujnicki, J.M. (deposition date: 2013-10-08, release date: 2014-01-22, Last modification date: 2024-02-28)

Primary citation

Smietanski, M.,Werner, M.,Purta, E.,Kaminska, K.H.,Stepinski, J.,Darzynkiewicz, E.,Nowotny, M.,Bujnicki, J.M.
Structural analysis of human 2'-O-ribose methyltransferases involved in mRNA cap structure formation.
Nat Commun, 5:3004-3004, 2014

PubMed 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.

PubMed: 24402442
DOI: 10.1038/ncomms4004

Experimental method

X-RAY DIFFRACTION (2.35 Å)