Base-modified donor analogues reveal novel dynamic features of a glycosyltransferase

Background: Modified UDP-Gal donor substrates with 5-formylthienyl and 5-phenyl substituents on the uracil base exhibit differential inhibition patterns for glycosyltransferases. Results: Structural studies reveal a new enzyme loop folding mode for the 5-formylthienyl analogue. Conclusion: Differential inhibition is attributed to alternate enzyme conformational changes and interactions with the respective inhibitors. Significance: The conformational plasticity of glycosyltransferases can be exploited in designing novel inhibitors.