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Nat Chem Biol. 2011 Oct 9;7(11):827-33. doi: 10.1038/nchembio.673.

The proteoglycan bikunin has a defined sequence.

Author information

1
Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, New York, USA.

Abstract

Proteoglycans are complex glycoconjugates that regulate critical biological pathways in all higher organisms. Bikunin, the simplest proteoglycan, with a single glycosaminoglycan chain, is a serine protease inhibitor used to treat acute pancreatitis. Unlike nucleic acids and proteins, whose synthesis is template driven, Golgi-synthesized glycosaminoglycans are not believed to have predictable or deterministic sequences. Bikunin peptidoglycosaminoglycans were prepared and fractionated to obtain a collection of size-similar and charge-similar chains. Fourier transform mass spectral analysis identified a small number of parent molecular ions corresponding to monocompositional peptidoglycosaminoglycans. Fragmentation using collision-induced dissociation unexpectedly afforded a single sequence for each monocompositional parent ion, unequivocally demonstrating the presence of a defined sequence. The biosynthetic pathway common to all proteoglycans suggests that even more structurally complex proteoglycans, such as heparan sulfate, may have defined sequences, requiring a readjustment in the understanding of information storage in complex glycans.

Comment in

PMID:
21983600
PMCID:
PMC3197799
DOI:
10.1038/nchembio.673
[Indexed for MEDLINE]
Free PMC Article

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