UDP-GalNAc:polypeptide N-Acetylgalactosaminyltransferases (GalNAcTs) catalyze the transfer of N-Acetylgalactosamine (GalNAc) from UDP-GalNAc to a threonine or serine residue in the first step of forming mucin-type glycoproteins. Certain GalNAcTs recognize and modify unglycosylated, or “naked” proteins, but many of the enzymes in this family have a preference for modifying glycosylated substrates. This preference can be mediated by interactions between the catalytic domain of the GalNAcT and O-GalNAc modified residue, or between the conserved C-terminal lectin domain and the modified residue. In some enzymes, both domains simultaneously mediate substrate recognition. I am using structural and biochemical methods to probe the general mechanism of catalysis of GalNAcTs and to gain insight into the molecular basis for the differences in substrate recognition between the enzymes.
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.