Glucuronidase: Difference between revisions
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<StructureSection load='3vnz' size='340' side='right' caption=' | <StructureSection load='3vnz' size='340' side='right' caption='β-glucuronidase complex with glucouronic acid, glycerol and PO4 ion (PDB code [[3vnz]]).' scene=''> | ||
This tutorial illustrates the quaternary structures of the human and ''E. coli'' β-glucuronidase enzyme. | This tutorial illustrates the quaternary structures of the human and ''E. coli'' β-glucuronidase enzyme. | ||
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== Relevance == | == Relevance == | ||
The ''E. coli'' form of β-glucuronidase (<scene name='59/596447/E_coli_b-glucuronidase/1'>overall structure</scene>, PDB ID | 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<ref>PMID:9829738</ref>. | 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== | ||
Deficiencies in the human form of β-glucuronidase (<scene name='59/596447/Human_bglucuronidase/1'>overall structure</scene>, PDB ID | Deficiencies in the human form of β-glucuronidase (<scene name='59/596447/Human_bglucuronidase/1'>overall structure</scene>, PDB ID [[3hn3]]<ref>DOI:10.2210/pdb3hn3/pdb</ref>) 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. | ||
== Structural highlights == | == Structural highlights == | ||
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The structure of the enzyme contains both α-helix (blue) and β-sheet (yellow) forms of <scene name='59/596447/E_coli_b-glucuronidase3/1'>secondary structure</scene>, with the β-sheets arranged in β-barrels in an immunoglobulin-like fold. | The structure of the enzyme contains both α-helix (blue) and β-sheet (yellow) forms of <scene name='59/596447/E_coli_b-glucuronidase3/1'>secondary structure</scene>, with the β-sheets arranged in β-barrels in an immunoglobulin-like fold. | ||
The catalytic pocket of BGUS contains two Glu residues<ref>PMID:22367201</ref>. | The <scene name='59/596476/Cv/3'>catalytic pocket</scene> of BGUS contains <scene name='59/596476/Cv/4'>two catalytic Glu residues</scene><ref>PMID:22367201</ref>. | ||
== 3D Structures of glucuronidase == | |||
[[Glucuronidase 3D structures]] | |||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
