1H NMR spectroscopic studies establish that heparanase is a retaining glycosidase

Wilson, Jennifer C., Laloo, Andrew Elohim, Singh, Sanjesh and Ferro, Vito (2014) 1H NMR spectroscopic studies establish that heparanase is a retaining glycosidase. Biochemical and Biophysical Research Communications, 443 1: 185-188. doi:10.1016/j.bbrc.2013.11.079

Author Wilson, Jennifer C.
Laloo, Andrew Elohim
Singh, Sanjesh
Ferro, Vito
Title 1H NMR spectroscopic studies establish that heparanase is a retaining glycosidase
Journal name Biochemical and Biophysical Research Communications   Check publisher's open access policy
ISSN 0006-291X
Publication date 2014-01-03
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.bbrc.2013.11.079
Open Access Status Not yet assessed
Volume 443
Issue 1
Start page 185
End page 188
Total pages 4
Place of publication Philadelphia, PA, United States
Publisher Academic Press
Language eng
Subject 1304 Biophysics
1303 Biochemistry
1312 Molecular Biology
1307 Cell Biology
Abstract Heparanase is an endo-β-glucuronidase that cleaves heparan sulfate side chains of proteoglycans in basement membranes and the extracellular matrix (ECM). Heparanase is implicated in several diverse pathological processes associated with ECM degradation such as metastasis, inflammation and angiogenesis and is thus an important target for anti-cancer and anti-inflammatory drug discovery. Heparanase has been classed as belonging to the clan A glycoside hydrolase family 79 based on sequence analysis, secondary structure predictions and mutagenic analysis, and thus it has been inferred that it is a retaining glycosidase. However, there has been no direct experimental evidence to support this conclusion. Herein we describe 1H NMR spectroscopic studies of the hydrolysis of the pentasaccharide substrate fondaparinux by heparanase, and provide conclusive evidence that heparanase hydrolyses its substrate with retention of configuration and is thus established as a retaining glycosidase. Knowledge of the mechanism of hydrolysis may have implications for future design of inhibitors for this important drug target.
Keyword Fondaparinux
Glycosidase mechanisms
NMR spectroscopy
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online: 26 November 2013.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 9 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 07 Jan 2014, 10:18:25 EST by System User on behalf of School of Chemistry & Molecular Biosciences