Structural insights into heparanase activity using a fluorogenic heparan sulfate disaccharide

TY - JOUR

T1 - Structural insights into heparanase activity using a fluorogenic heparan sulfate disaccharide

AU - Wu, Liang

AU - Wimmer, Norbert

AU - Davies, Gideon J.

AU - Ferro, Vito

PY - 2020/11/18

Y1 - 2020/11/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85096078189&partnerID=8YFLogxK

U2 - 10.1039/d0cc05932c

DO - 10.1039/d0cc05932c

M3 - Article

C2 - 33073275

AN - SCOPUS:85096078189

SN - 1359-7345

VL - 56

SP - 13780

EP - 13783

JO - Chemical Communications

JF - Chemical Communications

IS - 89

ER -