6JQ5

The structure of Hatchet Ribozyme

Summary for 6JQ5

• Entry DOI: 10.2210/pdb6jq5/pdb
• Descriptor: RNA (82-MER), MAGNESIUM ION (3 entities in total)
• Functional Keywords: ribozyme, non-coding rna, hatchet, cleavage, catalysis, rna
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 52785.64

Authors

Ren, A.,Zheng, L. (deposition date: 2019-03-29, release date: 2019-06-12, Last modification date: 2023-11-22)

Primary citation

Zheng, L.,Falschlunger, C.,Huang, K.,Mairhofer, E.,Yuan, S.,Wang, J.,Patel, D.J.,Micura, R.,Ren, A.
Hatchet ribozyme structure and implications for cleavage mechanism.
Proc.Natl.Acad.Sci.USA, 116:10783-10791, 2019

PubMed Abstract: Small self-cleaving ribozymes catalyze site-specific cleavage of their own phosphodiester backbone with implications for viral genome replication, pre-mRNA processing, and alternative splicing. We report on the 2.1-Å crystal structure of the hatchet ribozyme product, which adopts a compact pseudosymmetric dimeric scaffold, with each monomer stabilized by long-range interactions involving highly conserved nucleotides brought into close proximity of the scissile phosphate. Strikingly, the catalytic pocket contains a cavity capable of accommodating both the modeled scissile phosphate and its flanking 5' nucleoside. The resulting modeled precatalytic conformation incorporates a splayed-apart alignment at the scissile phosphate, thereby providing structure-based insights into the in-line cleavage mechanism. We identify a guanine lining the catalytic pocket positioned to contribute to cleavage chemistry. The functional relevance of structure-based insights into hatchet ribozyme catalysis is strongly supported by cleavage assays monitoring the impact of selected nucleobase and atom-specific mutations on ribozyme activity.

PubMed: 31088965
DOI: 10.1073/pnas.1902413116

Experimental method

X-RAY DIFFRACTION (2.059 Å)