Crystal Structure of an RNA-cleaving DNAzyme

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Dec 10

PMID 29222499

Citations 51

Authors

Hehua Liu

Xiang Yu

Yiqing Chen

Jing Zhang

Baixing Wu

Lina Zheng

Phensinee Haruehanroengra

Rui Wang

Suhua Li

Jinzhong Lin

Jixi Li

Jia Sheng

Zhen Huang

Jinbiao Ma

Jianhua Gan

Affiliations

Soon will be listed here.

Abstract

In addition to storage of genetic information, DNA can also catalyze various reactions. RNA-cleaving DNAzymes are the catalytic DNAs discovered the earliest, and they can cleave RNAs in a sequence-specific manner. Owing to their great potential in medical therapeutics, virus control, and gene silencing for disease treatments, RNA-cleaving DNAzymes have been extensively studied; however, the mechanistic understandings of their substrate recognition and catalysis remain elusive. Here, we report three catalytic form 8-17 DNAzyme crystal structures. 8-17 DNAzyme adopts a V-shape fold, and the Pb cofactor is bound at the pre-organized pocket. The structures with Pb and the modification at the cleavage site captured the pre-catalytic state of the RNA cleavage reaction, illustrating the unexpected Pb-accelerated catalysis, intrinsic tertiary interactions, and molecular kink at the active site. Our studies reveal that DNA is capable of forming a compacted structure and that the functionality-limited bio-polymer can have a novel solution for a functional need in catalysis.

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