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Energetic Basis of AGCGA‐Rich DNA Folding into a Tetrahelical Structure
Author(s) -
Hadži San,
Kocman Vojč,
Oblak Domen,
Plavec Janez,
Lah Jurij
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201813502
Subject(s) - folding (dsp implementation) , stacking , dna , chemistry , biophysics , base pair , g quadruplex , flexibility (engineering) , molecule , crystallography , computational biology , biology , biochemistry , organic chemistry , electrical engineering , engineering , statistics , mathematics
It was recently discovered that, besides well‐known G‐quadruplexes and i‐motifs, DNA may adopt another type of noncanonical structure called AGCGA‐quadruplexes. Here, the folding of the VK2 fragment from the regulatory region of the PLEKHG3 gene is studied and, for the first time, the energetic contributions that stabilize this unique fold are described. Similarly to the B‐DNA, it is stabilized by hydrophobic desolvation and, in contrast to G‐quadruplexes, also by specific binding of water molecules. Compared to B‐DNA, VK2 folding is enthalpically less favorable due to poorer base‐stacking interactions, resulting in substantial conformational flexibility. This entropically favorable conformational “breathing” stabilizes the AGCGA‐quadruplexes. In conclusion, AGCGA‐quadruplexes have a distinguishing thermodynamic fingerprint and the corresponding driving forces enabling their folding are consistent with the observed structural features.