By the same authors

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

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Publication details

Title of host publicationAdvances in Experimental Medicine and Biology
DatePublished - 2020
Pages139-167
Number of pages29
PublisherSpringer
Original languageEnglish

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1221
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Abstract

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.

Bibliographical note

Publisher Copyright:
© 2020, Springer Nature Switzerland AG.

    Research areas

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

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