A small-molecule switch for Golgi sulfotransferases

Christopher L. De Graffenried, Scott T. Laughlin, Jennifer J. Kohler, Carolyn R. Bertozzi

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


The study of glycan function is a major frontier in biology that could benefit from small molecules capable of perturbing carbohydrate structures on cells. The widespread role of sulfotransferases in modulating glycan function makes them prime targets for small-molecule modulators. Here, we report a system for conditional activation of Golgi-resident sulfotransferases using a chemical inducer of dimerization. Our approach capitalizes on two features shared by these enzymes: their requirement of Golgi localization for activity on cellular substrates and the modularity of their catalytic and localization domains. Fusion of these domains to the proteins FRB and FKBP enabled their induced assembly by the natural product rapamycin. We applied this strategy to the GlcNAc-6-sulfotransferases GlcNAc6ST-1 and GlcNAc6ST-2, which collaborate in the sulfation of L-selectin ligands. Both the activity and specificity of the inducible enzymes were indistinguishable from their WT counterparts. We further generated rapamycin-inducible chimeric enzymes comprising the localization domain of a sulfotransferase and the catalytic domain of a glycosyltransferase, demonstrating the generality of the system among other Golgi enzymes. The approach provides a means for studying sulfate-dependent processes in cellular systems and, potentially, in vivo.

Original languageEnglish (US)
Pages (from-to)16715-16720
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number48
StatePublished - Nov 30 2004


  • Chemical inducer of dimerization
  • L-selectin
  • Rapamycin

ASJC Scopus subject areas

  • General


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