Date of Award
Doctor of Philosophy
Chemical and Biological Engineering
Peter J. Reilly
Glycoside hydrolases (GHs) are enzymes that catalyze the hydrolysis of the glycosidic bond between two carbohydrate residues or a carbohydrate unit linked to a non-carbohydrate aglycon unit. Despite years of research dedicated to GHs, there are still several mechanistic details, relevant for individual GH enzymes, that remain to be investigated. In this work, a computational analysis of the detailed mechanism of several GHs is presented. QM/MM metadynamics simulations of two glycoside hydrolases, GH8 endoglucanase and GH43 β-xylosidase, give insight into the enzymatic deconstruction of the plant cell wall, and the detailed reaction mechanism of both enzymes. In addition, an investigation of the GH-imposed twisting of substrate glycosidic bonds in 14 different GH families is presented. Finally, a QM/MM metadynamics simulation of Golgi α-mannosidase unravels the hydrolysis mechanism of this enzyme, which is a target against breast, colon and skin cancer.
Petersen, Luis, "Catalytic strategies of glycoside hydrolases" (2010). Graduate Theses and Dissertations. 11144.