title: Altered biochemical specificity of G-quadruplexes with mutated tetrads.
abstract: 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.
authors: Institute of Organic Chemistry and Biochemistry ASCR, Prague 166 10, Czech Republic.|Charles University in Prague, Faculty of Science, Prague 128 44, Czech Republic.
authors: Kateřina
authors: K
authors: Švehlová
authors: Cancer Center and Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors: Michael S
authors: MS
authors: Lawrence
authors: Institute of Organic Chemistry and Biochemistry ASCR, Prague 166 10, Czech Republic.
authors: Lucie
authors: L
authors: Bednárová
authors: Institute of Organic Chemistry and Biochemistry ASCR, Prague 166 10, Czech Republic curtis@uochb.cas.cz.
authors: Edward A
authors: EA
authors: Curtis
mesh_terms: D001483:Base Sequence; D002942:Circular Dichroism; D054856:G-Quadruplexes; D015894:Genome, Human; D006160:Guanosine Triphosphate / Q000737:chemistry; D006801:Humans; D009154:Mutation; D009841:Oligonucleotides / Q000737:chemistry
chemical_list: D009841:Oligonucleotides; D006160:Guanosine Triphosphate