TY  - INPR
A1  - Scheitl, Carolin P. M.
A1  - Mieczkowski, Mateusz
A1  - Schindelin, Hermann
A1  - Höbartner, Claudia
T1  - Structure and mechanism of the methyltransferase ribozyme MTR1
T2  - Nature Chemical Biology
N2  - RNA-catalysed RNA methylation was recently shown to be part of the catalytic repertoire of ribozymes. The methyltransferase ribozyme MTR1 catalyses the site-specific synthesis of 1-methyladenosine (m\(^1\)A) in RNA, using O\(^6\)-methylguanine (m\(^6\)G) as methyl group donor. Here we report the crystal structure of MTR1 at a resolution of 2.8 Å, which reveals a guanine binding site reminiscent of natural guanine riboswitches. The structure represents the postcatalytic state of a split ribozyme in complex with the m1A-containing RNA product and the demethylated cofactor guanine. The structural data suggest the mechanistic involvement of a protonated cytidine in the methyl transfer reaction. A synergistic effect of two 2'-O-methylated ribose residues in the active site results in accelerated methyl group transfer. Supported by these results, it seems plausible that modified nucleotides may have enhanced early RNA catalysis and that metabolite-binding riboswitches may resemble inactivated ribozymes that have lost their catalytic activity during evolution.
KW  - Methyltransferase Ribozyme MTR1
KW  - Crystal structure of MTR1
KW  - RNA-catalyzed RNA methylation
KW  - X-ray crystallography
KW  - RNA
Y1  - 2022
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/27217
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-272170
ER  -