Comparison of the Structures and Mechanisms of the Pistol and Hammerhead Ribozymes

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2019 Apr 25

PMID 31017785

Citations 23

Authors

Timothy J Wilson

Yijin Liu

Nan-Sheng Li

Qing Dai

Joseph A Piccirilli

David M J Lilley

Affiliations

Soon will be listed here.

Abstract

Comparison of the secondary and three-dimensional structures of the hammerhead and pistol ribozymes reveals many close similarities, so in this work we have asked if they are mechanistically identical. We have determined a new crystal structure of the pistol ribozyme and have shown that G40 acts as general base in the cleavage reaction. The conformation in the active site ensures an in-line attack of the O2' nucleophile, and the conformation at the scissile phosphate and the position of the general base are closely similar to those in the hammerhead ribozyme. However, the two ribozymes differ in the nature of the general acid. 2'-Amino substitution experiments indicate that the general acid of the hammerhead ribozyme is the O2' of G8, while that of the pistol ribozyme is a hydrated metal ion. The two ribozymes are related but mechanistically distinct.

Citing Articles

The Role of General Acid Catalysis in the Mechanism of an Alkyl Transferase Ribozyme.

Wilson T, McCarthy E, Ekesan S, Giese T, Li N, Huang L ACS Catal. 2024; 14(20):15294-15305.

PMID: 39444533 PMC: 11494507. DOI: 10.1021/acscatal.4c04571.

The structure and catalytic mechanism of a pseudoknot-containing hammerhead ribozyme.

Zhan X, Wilson T, Li Z, Zhang J, Yang Y, Lilley D Nat Commun. 2024; 15(1):6628.

PMID: 39103372 PMC: 11300833. DOI: 10.1038/s41467-024-50892-y.

RNA structure determination: From 2D to 3D.

Deng J, Fang X, Huang L, Li S, Xu L, Ye K Fundam Res. 2024; 3(5):727-737.

PMID: 38933295 PMC: 11197651. DOI: 10.1016/j.fmre.2023.06.001.

Scaling Catalytic Contributions of Small Self-Cleaving Ribozymes.

Egger M, Bereiter R, Mair S, Micura R Angew Chem Weinheim Bergstr Ger. 2024; 134(41):e202207590.

PMID: 38505292 PMC: 10946891. DOI: 10.1002/ange.202207590.

Identification of Hammerhead-variant ribozyme sequences in SARS-CoV-2.

Liu G, Jiang H, Chen D, Murchie A Nucleic Acids Res. 2024; 52(6):3262-3277.

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