The catalytic mechanism of the RNA methyltransferase METTL3.

ABSTRACT: The complex of methyltransferase-like proteins 3 and 14 (METTL3-14) is the major enzyme that deposits N⁶-methyladenosine (m⁶A) modifications on messenger RNA (mRNA) in humans. METTL3-14 plays key roles in various biological processes through its methyltransferase (MTase) activity. However, little is known about its substrate recognition and methyl transfer mechanism from its cofactor and methyl donor S-adenosylmethionine (SAM). Here, we study the MTase mechanism of METTL3-14 by a combined experimental and multiscale simulation approach using bisubstrate analogues (BAs), conjugates of a SAM-like moiety connected to the N⁶-atom of adenosine. Molecular dynamics simulations based on crystal structures of METTL3-14 with BAs suggest that the Y406 side chai

SUBMITTER: Corbeski I 

PROVIDER: S-EPMC10932547 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature