Study of Reaction Mechanisms of Bacterial Glycosyltransferases by Molecular Modelling

Presentation by: Július Zemaník

Abstract:

Fucosyltransferases are inverting glycosyltransferases that transfer the fucosyl moiety from GDP-fucose to either galactose or N-acetyllactosamine. These fucosylated glycoconjugates are important in various physiological or pathophysiological processes.

The alpha-(1,3)-fucosyltransferase from H. pylori is responsible for the synthesis of Lewis antigens which have been proposed to play a role in the evasion of host immune surveillance. As a result, the enzyme represents an interesting pharmacological target. Unfortunately, the reaction mechanism of this enzyme remains unknown.

We have utilized various state-of-the-arts methods of computational chemistry to better characterize this enzyme, including AlphaFold2 structure predictions, substrate docking using Simulated annealing, molecular simulations such as classical or QM/MM molecular dynamics simulations, and preliminary free energy calculations. In this presentation, we present an overview of the results of our studies.