Structural insights in mammalian sialyltransferases and fucosyltransferases: We have come a long way, but it is still a long way down

Mammalian cell surfaces are modified with complex arrays of glycans that play major roles in health and disease. Abnormal glycosylation is a hallmark of cancer; terminal sialic acid and fucose in particular have high levels in tumor cells, with positive implications for malignancy. Increased sialylation and fucosylation are due to the upregulation of a set of sialyltransferases (STs) and fucosyltransferases (FUTs), which are potential drug targets in cancer. In the past, several advances in glycostructural biology have been made with the determination of crystal structures of several important STs and FUTs in mammals. Additionally, how the independent evolution of STs and FUTs occurred with a limited set of global folds and the diverse modular ability of catalytic domains toward substrates has been elucidated. This review highlights advances in the understanding of the structural architecture, substrate binding interactions, and catalysis of STs and FUTs in mammals. While this general understanding is emerging, use of this information to design inhibitors of STs and FUTs will be helpful in providing further insights into their role in the manifestation of cancer and developing targeted therapeutics in cancer.

Grewal, R. K., Shaikh, A. R., Gorle, S., Kaur, M., Videira, P. A., Cavallo, L., & Chawla, M. (2021). Structural Insights in Mammalian Sialyltransferases and Fucosyltransferases: We Have Come a Long Way, but It Is Still a Long Way Down. Molecules, 26(17), 5203. doi:10.3390/molecules26175203

The APC was funded by King Abdullah University of Science and Technology. M.C.: L.C. and A.R.S. acknowledge the King Abdullah University of Science and Technology (KAUST) for support. We thank Romina Oliva, University of Parthenope (Naples), for helpful comments. Thanks to the STEMskills Research and Education Lab team members for support.




Additional Links

Permanent link to this record