Building 30, Room 524
Bethesda, MD 20892
We study a family of glycosyltransferases termed GalNAc-Ts, which catalyze the transfer of N-Acetylgalactosamine (GalNAc) from UDP-GalNAc to a threonine or serine on a protein. Several GalNAc-Ts are associated with cancer and neurological disorders, but the specific substrates for many of these enzymes have not been identified, and thus the roles of GalNAc-Ts in health and disease remain elusive. GalNAc-Ts do not recognize a single consensus sequence in their substrates. Instead, diverse substrate binding preferences are encoded within non-conserved regions of the enzymes. We are investigating the molecular basis of the substrate preferences of GalNAc-Ts, to identify their substrates and better understand their biological functions.
We are also interested in bacterial glycosyltransferases involved in capsular polysaccharide (CPS) synthesis. CPSs are important for pathogenesis and are targets for antimicrobials. Understanding the synthesis machinery will help to identify potential drug targets that can inhibit CPS synthesis.
Dr. Nadine Samara received her PhD in Molecular Biophysics from The Johns Hopkins School of Medicine in 2012, where she received the Alice Showalter Reynolds Award for her work in structural biology. She continued her work in structural enzymology as an NIGMS-PRAT Fellow at the NIH and then transitioned to her Staff Scientist Position at NIDCR in 2015, where she continues to use structural and biochemical methods to probe enzyme function.
- Ji, S.*, Samara, N. L.*, Revoredo, L., Zhang, L., Tran, D. T., Muirhead, K., Tabak, L. A., Ten Hagen, K. G. (2018). A molecular switch orchestrates enzyme specificity and secretory granule morphology. Nature Communications, 9, 3508.
- Samara, N. L., & Yang, W. (2018). Cation trafficking propels RNA hydrolysis. Nature Structural & Molecular Biology, 25(8), 715–721.
- Samara NL, Gao Y, Wu J, Yang W (2017). Detection of Reaction Intermediates in Mg2+-Dependent DNA Synthesis and RNA Degradation by Time-Resolved X-Ray Crystallography. Methods Enzymol., 592, pp.283-327.
- Li C.L., Golebiowski F.M., Onishi Y., Samara N.L., Sugasawa K, Yang W. (2015). Tripartite DNA Lesion Recognition and Verification by XPC, TFIIH, and XPA in Nucleotide Excision Repair. Molecular Cell, vol. 59, issue 6, pp. 1025-34.
- Samara, N.L., Ringel, A.E., and Wolberger, C. (2012). A Role for Inter-subunit Interactions in Maintaining SAGA Deubiquitinating Module Structure and Activity. Structure, vol. 20, issue 8, pp.1414-24.
- Samara, N.L. and Wolberger, C. (2011). A New Chapter in the Transcription SAGA. Current Opinions in Structural Biology, vol. 21, issue 6, pp. 767-74.
- Samara, N.L., Datta, A.B., Berndsen, C.E., Zhang, X., Yao, T., Cohen, R.E., Wolberger, C. (2010). Structural Insights into the Assembly and Function of the SAGA Deubiquitinating Module. Science, vol. 328, pp.1025-29.