GUSB Human

Human beta-Glucuronidase is synthesized as an 80 kDa monomer consisting of 653 amino acids. After proteolysis, it forms a 78 kDa monomer . The enzyme exists as a 332 kDa homotetramer and contains several notable structural formations, including a type of beta-barrel known as a jelly roll barrel and a TIM barrel . The enzyme’s active site includes key residues such as Glu451, Tyr504, and Glu540, which are essential for its catalytic activity .

The mechanism of catalysis involves the hydrolysis of beta-D-glucuronic acid residues. The enzyme’s activity is facilitated by two acidic residues, Glu540 and Glu451, which act as the nucleophilic and acidic residues, respectively . Tyr504 also plays a crucial role in the catalytic process .

Beta-Glucuronidase is essential for the stepwise degradation of glucuronic acid-containing glycosaminoglycans . This degradation process is vital for maintaining the structural integrity and function of the extracellular matrix and cell membranes. The enzyme’s activity is crucial in various physiological processes, including the breakdown of heparan sulfate, chondroitin sulfate, and hyaluronan .

In the human gut, beta-Glucuronidase converts conjugated bilirubin to its unconjugated form, which is then reabsorbed . The enzyme is also present in breast milk, contributing to neonatal jaundice .

Recombinant human beta-Glucuronidase is produced using advanced biotechnological methods. It is typically expressed in a mouse myeloma cell line (NS0) and purified to high levels of purity . The recombinant enzyme is used in various research and clinical applications, including the study of lysosomal storage diseases and the development of therapeutic interventions .

The recombinant enzyme is supplied as a filtered solution in Tris and NaCl and is stable for several months when stored at appropriate temperatures . It is used in assays to measure its ability to hydrolyze specific substrates, such as 4-methylumbelliferyl-beta-D-glucuronide .