Molecular Aspects of Heparanase Interaction with Heparan Sulfate, Heparin and Glycol Split Heparin.

Abstract:

:Heparanase is the principal enzyme that degrades heparan sulfate (HS) in both physiological (HS turnover) and pathological (tumor metastasis, inflammation) cell conditions, catalysing the hydrolysis of the β-1-4 glycosidic bond in -GlcUA-β(1-4)-GlcNX-. Despite efforts to define the minimum trisaccharide sequence that allows glycans to be recognized by heparanase, a rigorous "molecular code" by which the enzyme reads and degrades HS chains has not been identified. The X-ray diffraction model of heparanase, resolved by Wu et al (2015), revealed a complex between the trisaccharide GlcNS6S-GlcUA-GlcNS6S and heparanase. Efforts are ongoing to better understand how HS mimetics longer than three residues are recognized by heparanase before being hydrolyzed or inhibit the enzyme. It is also important to consider the flexibility of the enzyme active site, a feature that opens up the development of heparanase inhibitors with structures significantly different from HS or heparin. This chapter reviews the state-of-the-art knowledge about structural aspects of heparanase activities in terms of substrate recognition, mechanism of hydrolysis, and inhibition.

journal_name

Adv Exp Med Biol

authors

Elli S,Guerrini M

doi

10.1007/978-3-030-34521-1_6

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

169-188

eissn

0065-2598

issn

2214-8019

journal_volume

1221

pub_type

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