Department of Chemistry and Biochemistry, Al-Nahrain University
Abstract
xix, 390 leaves : ill. (chiefly col.) ; 29 cm + 1 CD-ROMThe integrity of the base pair sequence that makes up the information storage system of cells is
under continual assault. Two of the most prevalent forms of nucleobase damage are conversion of
cytosine to uracil, and guanine to 8-oxoguanine. Repair of these lesions is initiated by a specific
glycosylase that hydrolyzes the N-glycosidic (sugar–nucleobase) bond of the damaged
nucleotide. The present thesis uses advanced computational chemistry techniques to study the
mechanism of action of three glycosylases, namely human uracil–DNA glycosylase (hUNG2),
adenine–DNA glycosylase (MutY) and human 8-oxoguanine–DNA glycosylase (hOgg1).
Truncated active-site models treated entirely with quantum mechanics, and reaction potential
energy surfaces, provide detailed structural and energetic information regarding how these
enzymes catalyze deglycosylation of their substrates. From these results, a novel and informative
method for predicting the mechanism (e.g., degree of asychronicity) and relative rate is proposed
