Glucuronidase: Difference between revisions
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<StructureSection load='3hn3' size='340' side='right' caption='Ribbon diagram of glycosylated human βα-glucuronidase complex with MPD(PDB code [[3hn3]]).' scene=''> | <StructureSection load='3hn3' size='340' side='right' caption='Ribbon diagram of glycosylated human βα-glucuronidase complex with MPD(PDB code [[3hn3]]).' scene=''> | ||
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== Function == | == 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. '''α-glucuronidase''' catalyzes the conversion of α-D-glucuronoside to alcohol and D-glucuronate<ref>PMID: | '''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<ref>PMID:8599764</ref>. '''α-glucuronidase''' catalyzes the conversion of α-D-glucuronoside to alcohol and D-glucuronate<ref>PMID:12169619</ref>. | ||
== Relevance == | == Relevance == | ||
The ''E. coli'' form of β-glucuronidase (<scene name='59/596447/E_coli_b-glucuronidase/1'>overall structure</scene>, PDB ID 3LPF<ref>DOI:10.2210/pdb3lpf/pdb</ref>) 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. | The ''E. coli'' form of β-glucuronidase (<scene name='59/596447/E_coli_b-glucuronidase/1'>overall structure</scene>, PDB ID 3LPF<ref>DOI:10.2210/pdb3lpf/pdb</ref>) 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. | 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<ref>PMID:9829738</ref>. | ||
==Disease== | ==Disease== | ||
