9S1D

Crystal structure of the methyltransferase ribozyme 1 with two 2'O-methylation (MTR1m2)

Summary for 9S1D

• Entry DOI: 10.2210/pdb9s1d/pdb
• Descriptor: Chains: A, Chains: B, Chains: C, ... (7 entities in total)
• Functional Keywords: ribozyme, methyltransferase, 2'o-methylation, accelerated catalysis, rna
• Biological source: synthetic construct; More
• Total number of polymer chains: 3
• Total formula weight: 20107.82

Authors

Chen, H.-A.,Scheitl, C.P.M.,Hoebartner, C. (deposition date: 2025-07-18, release date: 2026-07-22, Last modification date: 2026-07-29)

Primary citation

Aupic, J.,Chen, H.A.,Scheitl, C.P.M.,Hobartner, C.,Magistrato, A.
A magic methyl effect in the active site of a methyltransferase ribozyme.
Nat Commun, 2026

PubMed Abstract: The chemical richness of RNAs is greatly enhanced by post-transcriptional modifications with RNA methylation as the most prominent type. RNA modifications modulate the stability, folding and interaction pattern of RNA molecules. Furthermore, emerging data suggests RNA modifications also directly regulate the activity of catalytic RNA molecules, i.e., ribozymes. Here, we employ classical and hybrid quantum-classical (QM/MM) molecular dynamics (MD) simulations to investigate the reaction mechanism of an artificial methyltransferase ribozyme MTR1. Importantly, we pinpoint how 2'-O-methylations of active site nucleotides synergistically enhance ribozyme activity by reducing the conformational flexibility of the ribose rings and rigidifying the active site. Finally, the herein reported crystal structure of the modified MTR1, solved at 2.6 Å resolution, validates the results of our simulations. Taken together, our work supports the purported central role of modified RNA for early RNA catalysis and may guide rational design of more efficient ribozymes.

PubMed: 42469241
DOI: 10.1038/s41467-026-75575-8

Experimental method

X-RAY DIFFRACTION (2.6 Å)