Structural and mechanistic investigations of protein S-glycosyltransferases

Daisuke Fujinami, Chantal V Garcia de Gonzalo, Subhanip Biswas, Yue Hao, Huan Wang, Neha Garg, Tiit Lukk, Satish K Nair, Wilfred A van der Donk

Research output: Contribution to journalArticlepeer-review


Attachment of sugars to nitrogen and oxygen in peptides is ubiquitous in biology, but glycosylation of sulfur atoms has only been recently described. Here, we characterize two S-glycosyltransferases SunS and ThuS that selectively glycosylate one of five Cys residues in their substrate peptides; substitution of this Cys with Ser results in a strong decrease in glycosylation activity. Crystal structures of SunS and ThuS in complex with UDP-glucose or a derivative reveal an unusual architecture in which a glycosyltransferase type A (GTA) fold is decorated with additional domains to support homodimerization. Dimer formation creates an extended cavity for the substrate peptide, drawing functional analogy with O-glycosyltransferases involved in cell wall biosynthesis. This extended cavity contains a sharp bend that may explain the site selectivity of the glycosylation because the target Cys is in a Gly-rich stretch that can accommodate the bend. These studies establish a molecular framework for understanding the unusual S-glycosyltransferases.

Original languageEnglish (US)
Pages (from-to)1740-1749.e6
JournalCell chemical biology
Issue number12
Early online dateJul 14 2021
StatePublished - Dec 16 2021


  • glycocin
  • bacteriocin
  • antibiotic
  • RiPPs
  • S-glycosyltransferase
  • crystallography
  • S-glycosylation

ASJC Scopus subject areas

  • Drug Discovery
  • Molecular Medicine
  • Molecular Biology
  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology


Dive into the research topics of 'Structural and mechanistic investigations of protein S-glycosyltransferases'. Together they form a unique fingerprint.

Cite this