Sialidase specificity determined by chemoselective modification of complex sialylated glycans

Randy B. Parker, Janet E. McCombs, Jennifer J. Kohler

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Sialidases hydrolytically remove sialic acids from sialylated glycoproteins and glycolipids. Sialidases are widely distributed in nature and sialidase-mediated desialylation is implicated in normal and pathological processes. However, mechanisms by which sialidases exert their biological effects remain obscure, in part because sialidase substrate preferences are poorly defined. Here we report the design and implementation of a sialidase substrate specificity assay based on chemoselective labeling of sialosides. We show that this assay identifies components of glycosylated substrates that contribute to sialidase specificity. We demonstrate that specificity of sialidases can depend on structure of the underlying glycan, a characteristic difficult to discern using typical sialidase assays. Moreover, we discovered that Streptococcus pneumoniae sialidase NanC strongly prefers sialosides containing the Neu5Ac form of sialic acid versus those that contain Neu5Gc. We propose using this approach to evaluate sialidase preferences for diverse potential substrates.

Original languageEnglish (US)
Pages (from-to)1509-1514
Number of pages6
JournalACS Chemical Biology
Volume7
Issue number9
DOIs
StatePublished - Sep 21 2012

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Neuraminidase
Polysaccharides
Assays
Substrates
Sialic Acids
Glycolipids
N-Acetylneuraminic Acid
Pathologic Processes
Substrate Specificity
Streptococcus pneumoniae
Labeling
Glycoproteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Sialidase specificity determined by chemoselective modification of complex sialylated glycans. / Parker, Randy B.; McCombs, Janet E.; Kohler, Jennifer J.

In: ACS Chemical Biology, Vol. 7, No. 9, 21.09.2012, p. 1509-1514.

Research output: Contribution to journalArticle

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