Structure and function of carbohydrate processing enzymes

Group leader: Tracey Gloster

Research overview

I am interested in the structure and function of eukaryotic carbohydrate processing enzymes. Obtaining a greater appreciation of how these enzymes assimilate or degrade carbohydrates is important in understanding the biological roles that carbohydrates play in cellular processes, and also how these processes malfunction in a number of diseases, such as cancer, lysosomal storage disorders, and neurodegenerative diseases.

I am currently investigating the enzymes responsible for the degradation of heparan sulphate, a component of the extracellular matrix. Using a combination of approaches, including molecular biology, protein production, X-ray crystallography, enzyme kinetics and cell culture, I aim to gain a greater understanding of these enzymes from a mechanistic and structural perspective. Hopefully this will lead to the development of tools, such as enzyme inhibitors, that can be used to probe the biological functions of the enzymes, and possibly also for therapeutic applications in the longer term.

Related links

Research group website

Publications

He, X, Pierce, O, Haselhorst, T, Kolarich, D, Packer, NH , Gloster, T , Vocadlo, DJ, Qian, Y, Brooks, D & Kermode, AR 2013, ' Characterization and downstream mannose phosphorylation of human recombinant α-L-iduronidase produced in Arabidopsis complex glycan-deficient (cgl) seeds ' Plant Biotechnology Journal , vol 11, no. 9, pp. 1034–1043.
Stubbs, KA, Bacik, J-P, Perley-Robertson, GE, Whitworth, GE , Gloster, TM , Vocadlo, DJ & Mark, BL 2013, ' The development of selective inhibitors of NagZ: increased susceptibility of Gram-negative bacteria to β-lactams ' ChemBioChem , vol 14, no. 15, pp. 1973-1981.
Cuskin, F, Flint, JE , Gloster, TM , Morland, C, Basle, A, Henrissat, B, Coutinho, PM, Strazzulli, A, Solovyova, AS, Davies, GJ & Gilbert, HJ 2012, ' How nature can exploit nonspecific catalytic and carbohydrate binding modules to create enzymatic specificity ' Proceedings of the National Academy of Sciences of the United States of America , vol 109, no. 51, pp. 20889-20894.
Lazarus, MB, Jiang, J , Gloster, TM , Zandberg, WF, Whitworth, GE, Vocadlo, DJ & Walker, S 2012, ' Structural snapshots of the reaction coordinate for O-GlcNAc transferase ' Nature Chemical Biology , vol 8, no. 12, pp. 966-968.
Gloster, TM 2012, ' Development of inhibitors as research tools for carbohydrate-processing enzymes ' Biochemical Society Transactions , vol 40, pp. 913-928.

Overview

Scientists associated with the thirty-two research groups that are affiliated with the Biomedical Sciences Research Complex perform highly innovative, multi-disciplinary research in eleven broad areas of biomedical research, employing state-of-the-art techniques to address key questions at the leading edge of the biomedical and biological sciences.

Follow the links on the left to view individual research groups associated with one or more of the eleven BSRC research areas.

Research areas

Scientists associated with the thirty-two research groups that are affiliated with the Biomedical Sciences Research Complex perform highly innovative, multi-disciplinary research in eleven broad areas of biomedical research, employing state-of-the-art techniques to address key questions at the leading edge of the biomedical and biological sciences.

Follow the links on the left to view individual research groups associated with one or more of the eleven BSRC research areas.

Research by academic schools

Research in the BSRC is conducted by thirty-two independent research groups based in the Schools of Biology, Chemistry, Physics and Astronomy, and Medicine. Follow the links on the left to view groups associated with each school.