Fig. 1.

CPT-11 metabolism and E. coli β-glucuronidase. (A) Intravenously administered CPT-11 is activated by carboxylesterases (CE) to SN-38, an antineoplastic topoisomerase I poison. Liver SN-38 is inactivated via glucuronidation to SN-38G by UDP-glucuronosyltransferase (UGT) enzymes and sent to the intestines. β-Glucuronidases (β-glucs) in the symbiotic GI bacteria remove the glucuronide as a carbon source, and active SN-38 in the intestinal lumen generates dose-limiting diarrhea. (B) Crystal structure of the E. coli β-glucuronidase tetramer at 2.5 Å resolution. (C) Four selective bacterial β-glucuronidase inhibitors identified via high-throughput screening.