Glucuronidase: Difference between revisions

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== Relevance ==

Deficiencies in the human form of β-glucuronidase (<scene name='59/596447/Human_bglucuronidase/1'>overall structure</scene>) 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.

Deficiencies in the human form of β-glucuronidase (<scene name='59/596447/Human_bglucuronidase/1'>overall structure</scene>, PDB ID 3HN3) 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 (<scene name='59/596447/E_coli_b-glucuronidase/1'>overall structure</scene>) 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) 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.

Glucuronidase: Difference between revisions

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 == Relevance ==
-Deficiencies in the human form of &beta;-glucuronidase (<scene name='59/596447/Human_bglucuronidase/1'>overall structure</scene>) 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.
+Deficiencies in the human form of &beta;-glucuronidase (<scene name='59/596447/Human_bglucuronidase/1'>overall structure</scene>, PDB ID 3HN3) 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 &beta;-glucuronidase (<scene name='59/596447/E_coli_b-glucuronidase/1'>overall structure</scene>) 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 &beta;-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 &beta;-glucuronidase (<scene name='59/596447/E_coli_b-glucuronidase/1'>overall structure</scene>, PDB ID 3LPF) 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 &beta;-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 &beta;-glucuronidase is desired to alleviate this side-effect of CPT-11 treatment, hopefully without inhibiting the human form of the enzyme.