Chapter Two Computational Glycobiology: Mechanistic Studies of Carbohydrate-Active Enzymes and Implication for Inhibitor Design

Publication date: 2017 Source:Advances in Protein Chemistry and Structural Biology, Volume 109 Author(s): Andrew P. Montgomery, Kela Xiao, Xingyong Wang, Danielle Skropeta, Haibo Yu Carbohydrate-active enzymes (CAZymes) are families of essential and structurally related enzymes, which catalyze the creation, modification, and degradation of glycosidic bonds in carbohydrates to maintain essentially all kingdoms of life. CAZymes play a key role in many biological processes underpinning human health and diseases (e.g., cancer, diabetes, Alzheimer's diseases, AIDS) and have thus emerged as important drug targets in the fight against pathogenesis. The realization of the full potential of CAZymes remains a significant challenge, relying on a deeper understanding of the molecular mechanisms of catalysis. Considering numerous unsettled questions in the literature, while with a large amount of structural, kinetic, and mutagenesis data available for CAZymes, there is a pressing need and an abundant opportunity for collaborative computational and experimental investigations with the aim to unlock the secrets of CAZyme catalysis at an atomic level. In this review, we briefly survey key methodology development in computational studies of CAZyme catalysis. This is complemented by selected case studies highlighting mechanistic insights provided by computational glycobiology. Implication for inhibitor design by mimicking the transition state is also illustrated for both glycosid...
Source: Advances in Protein Chemistry and Structural Biology - Category: Biochemistry Source Type: research