Glycobiology Advance Access originally published online on August 18, 2003
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Glycobiology, 2003, Vol. 13, No. 12 929-939
© 2003 Oxford University Press
Conformational studies on the MUC1 tandem repeat glycopeptides: implication for the enzymatic O-glycosylation of the mucin protein core
2 Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805; 3 Department of Biochemistry, Kansas State University, Manhattan, KS 66506; 4 Institute of Organic Chemistry, University of Hamburg, 20146 Hamburg, Germany; 5 Faculty of Health Sciences, School of Dentistry, University of Copenhagen, Copenhagen DK-2200, Denmark; 6 Institute of Biochemistry, Medical Faculty, University of Cologne, 50931 Cologne, Germany
Received on May 19, 2003; revised on August 1, 2003; accepted on August 4, 2003
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 
-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.
1 To whom correspondence should be addressed; e-mail: ssherm{at}unmc.edu
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