3lpf

Structure of E. coli beta-Glucuronidase bound with a novel, potent inhibitor 1-((6,7-dimethyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl)-1-(2-hydroxyethyl)-3-(3-methoxyphenyl)thiourea

spinqualitylabelsall models 3lpf, resolution 2.26Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3lpf is a 2 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.26Å Ligands: MSE, Z77 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BGLR_ECOLI Publication Abstract from PubMed The dose-limiting side effect of the common colon cancer chemotherapeutic CPT-11 is severe diarrhea caused by symbiotic bacterial beta-glucuronidases that reactivate the drug in the gut. We sought to target these enzymes without killing the commensal bacteria essential for human health. Potent bacterial beta-glucuronidase inhibitors were identified by high-throughput screening and shown to have no effect on the orthologous mammalian enzyme. Crystal structures established that selectivity was based on a loop unique to bacterial beta-glucuronidases. Inhibitors were highly effective against the enzyme target in living aerobic and anaerobic bacteria, but did not kill the bacteria or harm mammalian cells. Finally, oral administration of an inhibitor protected mice from CPT-11-induced toxicity. Thus, drugs may be designed to inhibit undesirable enzyme activities in essential microbial symbiotes to enhance chemotherapeutic efficacy. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme.,Wallace BD, Wang H, Lane KT, Scott JE, Orans J, Koo JS, Venkatesh M, Jobin C, Yeh LA, Mani S, Redinbo MR Science. 2010 Nov 5;330(6005):831-5. PMID:21051639 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glucuronidase Glucuronisidase 3D structures

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