Conformational studies on the MUC1 tandem repeat glycopeptides: Implication for the enzymatic O-glycosylation of the mucin protein core

Leo Kinarsky, Ganesh Suryanarayanan, Om Prakash, Hans Paulsen, Henrik Clausen, Franz Georg Hanisch, Michael A Hollingsworth, Simon Sherman

Research output: Contribution to journalArticle

44 Scopus citations


The tandem repeat of the MUC1 protein core is a major site of O-glycosylation that is catalyzed by several polypeptide GalNAc-transferases. To define structural features of the peptide substrates that contribute to acceptor substrate efficiency, solution structures of the 21-residue peptide AHGVTSAPDTRPAPGSTAPPA (AHG21) from the MUC1 protein core and four isoforms, glycosylated with α-N-acetylgalactosamine on corresponding Thr residues, AHG21 (T5), AHG21 (T10), AHG21 (T17), and AHG21 (T5, T17), were investigated by NMR spectroscopy and computational methods. NMR studies revealed that sugar attachment affected the conformational equilibrium of the peptide backbone near the glycosylated Thr residues. The clustering of the low-energy conformations for nonglycosylated and glycosylated counterparts within the VTSA, DTR, and GSTA fragments (including all sites of potential glycosylation catalyzed by GalNAc-T1, -T2, and -T4 transferases) showed that the glycosylated peptides display distinct structural propensities that may explain, in part, the differences in substrate specificities exhibited by these polypeptide GalNAc-transferases.

Original languageEnglish (US)
Pages (from-to)929-939
Number of pages11
Issue number12
Publication statusPublished - Dec 1 2003



  • Glycopeptide
  • NMR
  • O-glycosylation
  • Substrate specificity

ASJC Scopus subject areas

  • Biochemistry

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