An Overview of the Structure, Mechanism and Specificity of Human Heparanase

Liang Wu*, Gideon J. Davies

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter


The retaining endo-β-D-glucuronidase Heparanase (HPSE) is the primary mammalian enzyme responsible for breakdown of the glycosaminoglycan heparan sulfate (HS). HPSE activity is essential for regulation and turnover of HS in the extracellular matrix, and its activity affects diverse processes such as inflammation, angiogenesis and cell migration. Aberrant heparanase activity is strongly linked to cancer metastasis, due to structural breakdown of extracellular HS networks and concomitant release of sequestered HS-binding growth factors. A full appreciation of HPSE activity in health and disease requires a structural understanding of the enzyme, and how it engages with its HS substrates. This chapter summarizes key findings from the recent crystal structures of human HPSE and its proenzyme. We present details regarding the 3-dimensional protein structure of HPSE and the molecular basis for its interaction with HS substrates of varying sulfation states. We also examine HPSE in a wider context against related β-D-glucuronidases from other species, highlighting the structural features that control exo/endo − glycosidase selectivity in this family of enzymes.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
Number of pages29
Publication statusPublished - 2020

Publication series

NameAdvances in Experimental Medicine and Biology
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Bibliographical note

Publisher Copyright:
© 2020, Springer Nature Switzerland AG.


  • Cancer
  • CAZy
  • Extracellular matrix
  • GH79
  • Glycosaminoglycan
  • Glycosidase
  • Glycoside hydrolase
  • Heparan sulfate
  • Heparanase

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