Chemical and structural insight into the O-GlcNAc modification: targeting neurodegeneration Seminar

Research in the Davies group focusses on the conformational analysis of enzyme action (for recent example / review see Refs ^1,2), especially in the area of carbohydrate chemistry. In this seminar he will focus on the modification of intracellular proteins by serine and threonine-linked N-acetylglucosamine (the so-called "O-GlcNAc modification); one of the most exciting glycosylations of higher organisms. This process, in contrast to other N- and O-linked glycosylations, is dynamic and frequently acts reciprocally to protein phosphorylation. In the seminar Professor Davies will address the O-GlcNAc modification, from its discovery - through the physical organic and structural analysis³ of its reaction mechanism - to the development and application of mechanism-based inhibitors to probe the cellular roles of O-GlcNAc. Such compounds are showing great promise for the treatment of tauopathy-based neurodegenerative disease.⁴

References

(1) Williams et al., Angew Chemie Int Ed 2014, 53, 1087.

(2) Speciale et al., Curr Opin Struct Biol 2014, 28, 1.

(3) He et al., J Am Chem Soc 2010, 132, 1807.

(4) Yuzwa et al., Nature Chemical Biology 2008, 4, 483.

All welcome to attend