TY  - JOUR
A1  - Rangadurai, Atul
A1  - Zhou, Huiqing
A1  - Merriman, Dawn K.
A1  - Meiser, Nathalie
A1  - Liu, Bei
A1  - Shi, Honglue
A1  - Szymanski, Eric S.
A1  - Al-Hashimi, Hashim M.
T1  - Why are Hoogsteen base pairs energetically disfavored in A-RNA compared to B-DNA?
T2  - Nucleic acids research
N2  - A(syn)-U/T and G(syn)-C+ Hoogsteen (HG) base pairs (bps) are energetically more disfavored relative to Watson–Crick (WC) bps in A-RNA as compared to B-DNA by >1 kcal/mol for reasons that are not fully understood. Here, we used NMR spectroscopy, optical melting experiments, molecular dynamics simulations and modified nucleotides to identify factors that contribute to this destabilization of HG bps in A-RNA. Removing the 2′-hydroxyl at single purine nucleotides in A-RNA duplexes did not stabilize HG bps relative to WC. In contrast, loosening the A-form geometry using a bulge in A-RNA reduced the energy cost of forming HG bps at the flanking sites to B-DNA levels. A structural and thermodynamic analysis of purine-purine HG mismatches reveals that compared to B-DNA, the A-form geometry disfavors syn purines by 1.5–4 kcal/mol due to sugar-backbone rearrangements needed to sterically accommodate the syn base. Based on MD simulations, an additional penalty of 3–4 kcal/mol applies for purine-pyrimidine HG bps due to the higher energetic cost associated with moving the bases to form hydrogen bonds in A-RNA versus B-DNA. These results provide insights into a fundamental difference between A-RNA and B-DNA duplexes with important implications for how they respond to damage and post-transcriptional modifications.
KW  - structural biology
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50867
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-508672
SN  - 1362-4962
SN  - 0305-1048
SN  - 1362-4954
N1  - This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
VL  - 46
IS  - 20
SP  - 11099
EP  - 11114
PB  - Oxford Univ. Press
CY  - Oxford
ER  -