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

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Heparanase

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1221))

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.

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Authors and Affiliations

  1. Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, Milan, Italy

    Stefano Elli & Marco Guerrini

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  1. Stefano Elli
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  2. Marco Guerrini
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Correspondence to Marco Guerrini .

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Editors and Affiliations

  1. Technion Integrated Cancer Center (TICC) Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Haifa, Israel

    Israel Vlodavsky

  2. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA

    Ralph D. Sanderson

  3. Technion Integrated Cancer Center (TICC) Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Haifa, Israel

    Neta Ilan

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Elli, S., Guerrini, M. (2020). Molecular Aspects of Heparanase Interaction with Heparan Sulfate, Heparin and Glycol Split Heparin. In: Vlodavsky, I., Sanderson, R., Ilan, N. (eds) Heparanase. Advances in Experimental Medicine and Biology, vol 1221. Springer, Cham. https://doi.org/10.1007/978-3-030-34521-1_6

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