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Guanine to Inosine Substitution Leads to Large Increases in the Population of a Transient G·C Hoogsteen Base Pair
Author(s) -
Evgenia N. Nikolova,
Frederick Stull,
Hashim M. AlHashimi
Publication year - 2014
Publication title -
biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.43
H-Index - 253
eISSN - 1520-4995
pISSN - 0006-2960
DOI - 10.1021/bi5011909
Subject(s) - guanine , inosine , transient (computer programming) , base (topology) , chemistry , substitution (logic) , population , stereochemistry , biochemistry , mathematics , nucleotide , computer science , enzyme , medicine , environmental health , programming language , operating system , mathematical analysis , gene
We recently showed that Watson-Crick base pairs in canonical duplex DNA exist in dynamic equilibrium with G(syn)·C+ and A(syn)·T Hoogsteen base pairs that have minute populations of ∼1%. Here, using nuclear magnetic resonance R1ρ relaxation dispersion, we show that substitution of guanine with the naturally occurring base inosine results in an ∼17-fold increase in the population of transient Hoogsteen base pairs, which can be rationalized by the loss of a Watson-Crick hydrogen bond. These results provide further support for transient Hoogsteen base pairs and demonstrate that their population can increase significantly upon damage or chemical modification of the base.

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