Treatment of nonspecific DNA-protein contacts and application to the excision mechanism of a unique human DNA glycosylase
Date
2011
Authors
Rutledge, Lesley R
University of Lethbridge. Faculty of Arts and Science
Journal Title
Journal ISSN
Volume Title
Publisher
Lethbridge, Alta. : University of Lethbridge, Dept. of Chemistry and Biochemistry, c2011
Abstract
This thesis concentrates on understanding how individual nonspecific DNA–protein
contacts are used in the excision mechanism of the human DNA repair enzyme, alkyladenine
DNA glycosylase (AAG). Initially, studies focus on understanding the structure and
magnitude of these fundamentally different DNA–protein stacking and T-shaped
interactions to be applied to the active site of AAG. High-level ab initio techniques revealed
fundamental knowledge about the structure and magnitude of these distinctly different π+ and π contacts between (one or two) conjugated amino acid(s) and one nucleobase.
Additionally, the mechanism used by AAG to excise (neutral and cationic) damaged
nucleotides was investigated using a hybrid ONIOM approach. Reaction potential energy
surfaces reveal that AAG prefers to excise both neutral and cationic substrates through a
concerted mechanism, yet the nonspecific contacts present in the active site are only
catalytic for the cleavage of the neutral substrates.
Description
xvi, 195 leaves : ill. (some col.) ; 29 cm + 1 CD-ROM
Keywords
DNA ligases -- Research , DNA repair -- Research , DNA -- Methylation -- Research , Alkylation , Glycoproteins -- Research , Dissertations, Academic