Sandbox bcce8

This tutorial illustrates the quaternary structures of the human and E. coli β-glucuronidase enzyme.

Function

β-glucuronidase is a ubiquitous enzyme that catalyzes the hydrolysis of a glucuronide moiety from a variety of substrates. This enzyme is present throughout biological systems, including bacteria up through humans.

Relevance

Deficiencies in the human form of β-glucuronidase is associated with a disease known as Sly Syndrome (AKA Mucopolysaccharidosis VII -- MPS VII). This disease is characterized by mental retardation, short stature, macrocephaly, and enlarged joints. As is commonly seen with genetic disorders, patients with this disease present a spectrum of symptom severity, but the disease is always ultimately fatal.

The E. coli form of β-glucuronidase is associated with the side effects seen with administration of the cancer chemotherapy drug CPT-11. This drug gets converted to SN38, a topoisomerase inhibitor, by the liver. The body adds a glucuronide group to this molecule (now SN38-G) to mark it for elimination, which partially occurs through the intestine. Once in the intestine, bacterial β-glucuronidase cleaves the glucuronide from the SN38-G, releasing the SN38 into the intestinal lumen. The released SN38 prevents cell division, compromising the epithelial lining of the intestines, a painful and dangerous side-effect of CPT-11 administration.

Selective inhibition of bacterial β-glucuronidase is desired to alleviate this side-effect of CPT-11 treatment, hopefully without inhibiting the human form of the enzyme.

Structural highlights

This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.