heparanase activity

Definition

Target type: molecularfunction

Catalysis of the cleavage of heparan sulfate; can degrade both heparan sulfate and heparin glycosaminoglycan chains. [PMID:10916150]

Heparanase activity refers to the enzymatic cleavage of heparan sulfate (HS), a highly sulfated glycosaminoglycan (GAG) found on the cell surface and in the extracellular matrix (ECM). HS is a complex and diverse polysaccharide that interacts with a wide range of proteins, including growth factors, chemokines, and proteases, influencing a variety of cellular processes such as cell adhesion, migration, proliferation, and angiogenesis. Heparanase, the enzyme responsible for HS degradation, is a member of the endo-beta-D-glucuronidase family and exhibits a distinct mode of action compared to other GAG-degrading enzymes. Unlike hyaluronidases, which cleave hyaluronic acid, or chondroitinases, which cleave chondroitin sulfate, heparanase specifically targets the glycosidic linkage between glucuronic acid and N-acetylglucosamine residues within HS chains. This specific cleavage event results in the generation of HS fragments of varying sizes, which can have distinct biological activities. The precise mechanism of heparanase action involves a two-step process. Initially, heparanase binds to HS through its carbohydrate recognition domain, mediating an initial interaction with the substrate. Subsequently, the enzyme undergoes a conformational change, exposing its active site and allowing for the cleavage of the glycosidic bond. This process is facilitated by the presence of a specific amino acid sequence within heparanase, known as the "catalytic triad." The catalytic triad consists of three essential amino acids, typically aspartate, glutamate, and histidine, which work in concert to facilitate the hydrolysis of the glycosidic bond. Once cleaved, the HS fragments generated by heparanase can exhibit altered biological activities compared to the intact polysaccharide. These fragments can act as signaling molecules, modulating the activity of various growth factors, chemokines, and other proteins. Furthermore, the degradation of HS by heparanase can alter the structural integrity of the ECM, promoting cell migration and invasion. The release of HS fragments from the cell surface can also impact cell adhesion and signaling pathways. The activity of heparanase is tightly regulated, with a balance between its production and inhibition crucial for maintaining normal tissue homeostasis. Deregulation of heparanase activity has been implicated in a wide range of pathological conditions, including cancer, inflammation, and cardiovascular disease. In cancer, heparanase promotes tumor growth, angiogenesis, and metastasis by facilitating cell invasion and migration. In inflammatory diseases, heparanase contributes to tissue damage and immune cell recruitment. In cardiovascular disease, heparanase contributes to atherosclerosis and vascular remodeling. Therefore, heparanase represents a promising therapeutic target for a variety of diseases.'
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Proteins (1)

Compounds (10)