Structure and Inhibition of Microbiome β-Glucuronidases Essential to the Alleviation of Cancer Drug Toxicity

The selective inhibition of bacterial β-glucuronidases was recently shown to alleviate drug-induced gastrointestinal toxicity in mice, including the damage caused by the widely used anticancer drug irinotecan. Here, we report crystal structures of representative β-glucuronidases from the Firmicutes...

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Veröffentlicht in:	Chemistry & biology 2015-09, Vol.22 (9), p.1238-1249
Hauptverfasser:	Wallace, Bret D., Roberts, Adam B., Pollet, Rebecca M., Ingle, James D., Biernat, Kristen A., Pellock, Samuel J., Venkatesh, Madhu Kumar, Guthrie, Leah, O’Neal, Sara K., Robinson, Sara J., Dollinger, Makani, Figueroa, Esteban, McShane, Sarah R., Cohen, Rachel D., Jin, Jian, Frye, Stephen V., Zamboni, William C., Pepe-Ranney, Charles, Mani, Sridhar, Kelly, Libusha, Redinbo, Matthew R.
Format:	Artikel
Sprache:	eng
Schlagworte:	60 APPLIED LIFE SCIENCES Amino Acid Sequence Animals Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacokinetics Antineoplastic Agents - toxicity Bacterial Proteins - antagonists & inhibitors Bacterial Proteins - chemistry Bacterial Proteins - metabolism Bacteroides fragilis - enzymology Camptothecin - analogs & derivatives Camptothecin - chemistry Camptothecin - pharmacokinetics Camptothecin - toxicity chemotherapy-induced diarrhea Clostridium perfringens - enzymology Drug Screening Assays, Antitumor Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacokinetics Enzyme Inhibitors - toxicity Escherichia coli - enzymology Glucuronidase - antagonists & inhibitors Glucuronidase - chemistry Glucuronidase - metabolism Irinotecan Mice Mice, Inbred BALB C microbiota Microbiota - drug effects Models, Molecular Molecular Sequence Data NSAIDs Streptococcus agalactiae - enzymology
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