1. Academic Validation
  2. Mechanisms of the sialidase and trans-sialidase activities of bacterial sialyltransferases from glycosyltransferase family 80

Mechanisms of the sialidase and trans-sialidase activities of bacterial sialyltransferases from glycosyltransferase family 80

  • Glycobiology. 2016 Apr;26(4):353-9. doi: 10.1093/glycob/cwv105.
Kevin Mehr 1 Stephen G Withers 2
Affiliations

Affiliations

  • 1 Department of Chemistry and Centre for High-throughput Biology, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada.
  • 2 Department of Chemistry and Centre for High-throughput Biology, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada withers@chem.ubc.ca.
Abstract

Many important biological functions are mediated by complex glycan structures containing the nine-carbon sugar sialic acid (Sia) at terminal, non-reducing positions. Sia are introduced onto glycan structures by Enzymes known as sialyltransferases (STs). Bacterial STs from the Glycosyltransferase family GT80 are a group of well-studied Enzymes used for the synthesis of sialylated glycan structures. While highly efficient at sialyl transfer, these Enzymes also demonstrate sialidase and trans-sialidase activities for which there is some debate surrounding the corresponding enzymatic mechanisms. Here we propose a mechanism for STs from the Glycosyltransferase family GT80 in which sialidase and trans-sialidase activities occur through reverse sialylation of CMP. The resulting CMP-Sia is then enzymatically hydrolyzed or used as a donor in subsequent ST reactions resulting in sialidase and trans-sialidase activities, respectively. We provide evidence for this mechanism by demonstrating that CMP is required for sialidase and trans-sialidase activities and that its removal with Phosphatase ablates activity. We also confirm the formation of CMP-Sia using a coupled Enzyme assay. A clear understanding of the sialidase and trans-sialidase mechanisms for this class of Enzymes allows for more effective use of these Enzymes in the synthesis of glycoconjugates.

Keywords

glycoside synthesis; mechanism; sialoconjugates; sialyltransferase; trans-sialidase.

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