7L3R

23S Sarcin Ricin Loop with a 3-deazapurine A2670

Summary for 7L3R

• Entry DOI: 10.2210/pdb7l3r/pdb
• Descriptor: RNA (27-MER), GLYCEROL (3 entities in total)
• Functional Keywords: rna modification, ribosome, rna
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 8835.36

Authors

Ennifar, E.,Renard, E. (deposition date: 2020-12-18, release date: 2021-05-05, Last modification date: 2023-10-18)

Primary citation

Bereiter, R.,Himmelstoss, M.,Renard, E.,Mairhofer, E.,Egger, M.,Breuker, K.,Kreutz, C.,Ennifar, E.,Micura, R.
Impact of 3-deazapurine nucleobases on RNA properties.
Nucleic Acids Res., 49:4281-4293, 2021

PubMed Abstract: Deazapurine nucleosides such as 3-deazaadenosine (c3A) are crucial for atomic mutagenesis studies of functional RNAs. They were the key for our current mechanistic understanding of ribosomal peptide bond formation and of phosphodiester cleavage in recently discovered small ribozymes, such as twister and pistol RNAs. Here, we present a comprehensive study on the impact of c3A and the thus far underinvestigated 3-deazaguanosine (c3G) on RNA properties. We found that these nucleosides can decrease thermodynamic stability of base pairing to a significant extent. The effects are much more pronounced for 3-deazapurine nucleosides compared to their constitutional isomers of 7-deazapurine nucleosides (c7G, c7A). We furthermore investigated base pair opening dynamics by solution NMR spectroscopy and revealed significantly enhanced imino proton exchange rates. Additionally, we solved the X-ray structure of a c3A-modified RNA and visualized the hydration pattern of the minor groove. Importantly, the characteristic water molecule that is hydrogen-bonded to the purine N3 atom and always observed in a natural double helix is lacking in the 3-deazapurine-modified counterpart. Both, the findings by NMR and X-ray crystallographic methods hence provide a rationale for the reduced pairing strength. Taken together, our comparative study is a first major step towards a comprehensive understanding of this important class of nucleoside modifications.

PubMed: 33856457
DOI: 10.1093/nar/gkab256

Experimental method

X-RAY DIFFRACTION (1.01 Å)