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Publication Abstract from PubMed

Ribozymes that react with small-molecule probes have important applications in transcriptomics and chemical biology, such as RNA labeling and imaging. Understanding the structural basis for these RNA-modifying reactions will enable the development of better tools for studying RNA. Nevertheless, high-resolution structures and underlying catalytic mechanisms for members of this ribozyme class remain elusive. Here, we focus on a self-alkylating ribozyme that catalyzes nitrogen-carbon bond formation between a specific guanine and a 2,3-disubstituted epoxide substrate and report the crystal structures of a self-alkylating ribozyme, including both alkylated and apo forms, at 1.71-A and 2.49-A resolution, respectively. The ribozyme assumes an elongated hairpin-like architecture preorganized to accommodate the epoxide substrate in a hook-shaped conformation. Observed reactivity of substrate analogs together with an inverse, log-linear pH dependence of the reaction rate suggests a requirement for epoxide protonation, possibly assisted by the ether oxygens within the substrate.

Structural basis for substrate binding and catalysis by a self-alkylating ribozyme.,Krochmal D, Shao Y, Li NS, DasGupta S, Shelke SA, Koirala D, Piccirilli JA Nat Chem Biol. 2022 Apr;18(4):376-384. doi: 10.1038/s41589-021-00950-z. Epub 2022 , Jan 20. PMID:35058645^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.