9FN2

Crystal structure of the alkyltransferase ribozyme SAMURI co-crystallized with SAM

This is a non-PDB format compatible entry.

Summary for 9FN2

• Entry DOI: 10.2210/pdb9fn2/pdb
• Related: 9FN3
• Descriptor: SAMURI-SAM, MAGNESIUM ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (4 entities in total)
• Functional Keywords: alkylation ribozyme, sam, methylation, samuri, rna
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 38559.29

Authors

Chen, H.-A.,Okuda, T.,Lenz, A.-K.,Scheitl, C.P.M.,Schindelin, H.,Hoebartner, C. (deposition date: 2024-06-07, release date: 2025-01-22, Last modification date: 2025-02-05)

Primary citation

Chen, H.A.,Okuda, T.,Lenz, A.K.,Scheitl, C.P.M.,Schindelin, H.,Hobartner, C.
Structure and catalytic activity of the SAM-utilizing ribozyme SAMURI.
Nat.Chem.Biol., 2025

PubMed Abstract: Ribozymes that catalyze site-specific RNA modification have recently gained increasing interest for their ability to mimic methyltransferase enzymes and for their application to install molecular tags. Recently, we reported SAMURI as a site-specific alkyltransferase ribozyme using S-adenosylmethionine (SAM) or a stabilized analog to transfer a methyl or propargyl group to N of an adenosine. Here, we report the crystal structures of SAMURI in the postcatalytic state. The structures reveal a three-helix junction with the catalytic core folded into four stacked layers, harboring the cofactor and the modified nucleotide. Detailed structure-activity analyses explain the cofactor scope and the structural basis for site selectivity. A structural comparison of SAMURI with SAM riboswitches sheds light on how the synthetic ribozyme overcomes the strategies of natural riboswitches to avoid self-methylation. Our results suggest that SAM and its analogs may serve as substrates for various RNA-catalyzed reactions, for which the corresponding ribozymes remain to be identified.

PubMed: 39779902
DOI: 10.1038/s41589-024-01808-w

Experimental method

X-RAY DIFFRACTION (2.9 Å)