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Structural insights into heparanase activity using a fluorogenic heparan sulfate disaccharide

DOI: 10.1039/D0CC05932C DOI Help

Authors: Liang Wu (University of York) , Norbert Wimmer (The University of Queensland) , Gideon Davies (University of York) , Vito Ferro (The University of Queensland)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Chemical Communications , VOL 3

State: Published (Approved)
Published: October 2020
Diamond Proposal Number(s): 18598

Abstract: A synthetic heparan sulfate disaccharide has been assessed as a fluorogenic heparanase substrate, enabling enzyme turnover and inhibition kinetics measurements despite slow turnover. Crystal structures with human heparanase also provide the first ever observation of a substrate in an activated 1S3 conformation, highlighting previously unknown interactions involved in enzymatic processing. Our data provide insights into the heparanase catalytic mechanism, and will inform the design of improved heparanase substrates and inhibitors.

Subject Areas: Chemistry


Instruments: I04-Macromolecular Crystallography