Strukturní podstata biochemické specificity G-kvadruplexů

Sgallová, Ráchel

Title: Structural basis of G-qudruplex biochemical specificity Author: Ráchel Sgallová Department: Department of Low Temperature Physics Supervisor: Edward Arthur Curtis, Ph.D., Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Abstract: G-quadruplexes are noncanonical nucleic acid structures formed by stacked guanine tetrads. Despite their functional and structural diversity, a sin- gle consensus sequence is typically used to describe sequences with the potential to form G-quadruplex structures. We are interested in developing more specific sequence models for G-quadruplexes. In previous work, we functionally character- ized each sequence in a 496-member library of variants of a monomeric reference G-quadruplex for the ability to bind GTP, promote a model peroxidase reac- tion, generate intrinsic fluorescence, and to form multimers. In this study, we statistically characterized those results by PCA and identified some connections between primary sequence and biochemical function. Furthermore, we used NMR to obtain a broad overview of the structural features of this library. After deter- mining the 1 H NMR spectrum of each of these 496 sequences, spectra were sorted into multiple classes, most of which could be rationalized based on mutational patterns in the primary sequence....

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