SNAP output for PDB entry 6xjz [SNAP web server]

PDB-id

6xjz; SNAP-derived features in text and JSON formats; DNAproDB

Class

RNA-immune system

Method

X-ray (2.488 Å)

Summary

Crystal structure of a self-alkylating ribozyme - apo form

Reference

Krochmal D, Shao Y, Li NS, DasGupta S, Shelke SA, Koirala D, Piccirilli JA (2022): "Structural basis for substrate binding and catalysis by a self-alkylating ribozyme." Nat.Chem.Biol., 18, 376-384. doi: 10.1038/s41589-021-00950-z.

Abstract

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-Å and 2.49-Å 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.