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http://purl.uniprot.org/citations/12705903http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12705903http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12705903http://www.w3.org/2000/01/rdf-schema#comment"Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a neuron-specific ubiquitin recycling enzyme. A mutation at residue 93 and polymorphism at residue 18 within human UCH-L1 are linked to familial Parkinson's disease and a decreased Parkinson's disease risk, respectively. Thus, we constructed recombinant human UCH-L1 variants and examined their structure (using circular dichroism) and hydrolase activities. We confirmed that an I93M substitution results in a decrease in kcat (45.6%) coincident with an alteration in alpha-helical content. These changes may contribute to the pathogenesis of Parkinson's disease. In contrast, an S18Y substitution results in an increase in kcat (112.6%) without altering the circular dichroistic spectrum. These data suggest that UCH-L1 hydrolase activity may be inversely correlated with Parkinson's disease risk and that the hydrolase activity is protective against the disease. Furthermore, we found that oxidation of UCH-L1 by 4-hydroxynonenal, a candidate for endogenous mediator of oxidative stress-induced neuronal cell death, results in a loss of hydrolase activity. Taken together, these results suggest that further studies of altered UCH-L1 hydrolase function may provide new insights into a possible common pathogenic mechanism between familial and sporadic Parkinson's disease."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.org/dc/terms/identifier"doi:10.1016/s0006-291x(03)00555-2"xsd:string
http://purl.uniprot.org/citations/12705903http://purl.org/dc/terms/identifier"doi:10.1016/s0006-291x(03)00555-2"xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Aoki S."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Aoki S."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Li H."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Li H."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Hara Y."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Hara Y."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Wada K."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Wada K."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Nishikawa K."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Nishikawa K."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Noda M."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Noda M."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Osaka H."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Osaka H."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Wang Y.-L."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Wang Y.-L."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Amano T."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Amano T."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Kawamura R."xsd:string
http://purl.uniprot.org/citations/12705903http://purl.uniprot.org/core/author"Kawamura R."xsd:string