Human Heparanase

Heparanase, also known as HPSE, is an enzyme that acts both at the cell-surface and within the extracellular matrix to degrade polymeric heparan sulfate molecules into shorter chain length oligosaccharides. The protein is originally synthesised in an inactive 65 kDa proheparanase form in the golgi apparatus and transferred to late endosomes/lysosomes for transport to the cell-surface. In the lysosome it is proteolytically processed into its active form. Proteolytic processing results in the production of three products: a linker peptide, an 8 kDa proheparanase fragment, and a 50 kDa proheparanase fragment. The 8 kDa and 50 kDa fragments form a heterodimer and it is this heterodimer that constitutes the active heparanase molecule. The linker protein is so called because prior to its excision it physically links the 8 kDa and 50 kDa proheparanase fragments. Complete excision of the linker peptide appears to be a prerequisite to the complete activation of the heparanase enzyme. Crystal structures of both proheparanase and mature heparanase are available, showing that the linker peptide forms a large helical domain which blocks heparan sulfate molecules from interacting with heparanase. Removal of the linker reveals an extended cleft on the enzyme surface, which contains the heparanase active site.body{zoom:75%!important;}