Altered biochemical specificity of G-quadruplexes with mutated tetrads

0470632 - ÚOCHB 2017 RIV GB eng J - Journal Article
Švehlová, Kateřina - Lawrence, M. S. - Bednárová, Lucie - Curtis, Edward A.
Altered biochemical specificity of G-quadruplexes with mutated tetrads.
Nucleic Acids Research. Roč. 44, č. 22 (2016), s. 10789-10803. ISSN 0305-1048. E-ISSN 1362-4962
Institutional support: RVO:61388963
Keywords : G-quadruplex * G motif GTP aptamer * peroxidase deoxyribozyme
Subject RIV: CE - Biochemistry
Impact factor: 10.162, year: 2016
https://academic.oup.com/nar/article/44/22/10789/2333933/Altered-biochemical-specificity-of-G-quadruplexes

A fundamental motif in canonical nucleic acid structure is the base pair. Mutations that disrupt base pairs are typically destabilizing, but stability can often be restored by a second mutation that replaces the original base pair with an isosteric variant. Such concerted changes are a way to identify helical regions in secondary structures and to identify new functional motifs in sequenced genomes. In principle, such analysis can be extended to non-canonical nucleic acid structures, but this approach has not been utilized because the sequence requirements of such structures are not well understood. Here we investigate the sequence requirements of a G-quadruplex that can both bind GTP and promote peroxidase reactions. Characterization of all 256 variants of the central tetrad in this structure indicates that certain mutations can compensate for canonical G-G-G-G tetrads in the context of both GTP-binding and peroxidase activity. Furthermore, the sequence requirements of these two motifs are significantly different, indicating that tetrad sequence plays a role in determining the biochemical specificity of G-quadruplex activity. Our results provide insight into the sequence requirements of G-quadruplexes, and should facilitate the analysis of such motifs in sequenced genomes.
Permanent Link: http://hdl.handle.net/11104/0268213