| http://purl.uniprot.org/citations/21320589 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21320589 | http://www.w3.org/2000/01/rdf-schema#comment | "The aggregation of α-synuclein (α-Syn), the major component of intracellular Lewy body inclusions in dopaminergic neurons of the substantia nigra, plays a critical role in the etiology of Parkinson disease (PD). Long-term effects of redox-active transition metals (Cu, Fe) and oxidative chemical imbalance underlie the disease progression and neuronal death. In this work, we provide evidence that a brain metalloprotein, Zn₇-metallothionein-3 (Zn₇MT-3), possesses a dynamic role in controlling aberrant protein-copper interactions in PD. We examined the properties of the α-Syn-Cu(II) complex with regard to molecular oxygen, the biological reducing agent ascorbate, and the neurotransmitter dopamine. The results revealed that under aerobic conditions α-Syn-Cu(II) possesses catalytic oxidase activity. The observed metal-centered redox chemistry significantly promotes the production of hydroxyl radicals and α-Syn oxidation and oligomerization, processes considered critical for cellular toxicity. Moreover, we show that Zn₇MT-3, through Cu(II) removal from the α-Syn-Cu(II) complex, efficiently prevents its deleterious redox activity. We demonstrate that the Cu(II) reduction by thiolate ligands of Zn₇MT-3 and the formation of Cu(I)₄Zn₄MT-3, in which an unusual oxygen-stable Cu(I)₄-thiolate cluster is present, comprise the underlying molecular mechanism by which α-Syn and dopamine oxidation, α-Syn oligomerization, and ROS production are abolished. These studies provide new insights into the bioinorganic chemistry of PD."xsd:string |
| http://purl.uniprot.org/citations/21320589 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.freeradbiomed.2011.02.003"xsd:string |
| http://purl.uniprot.org/citations/21320589 | http://purl.uniprot.org/core/author | "Meloni G."xsd:string |
| http://purl.uniprot.org/citations/21320589 | http://purl.uniprot.org/core/author | "Vasak M."xsd:string |
| http://purl.uniprot.org/citations/21320589 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21320589 | http://purl.uniprot.org/core/name | "Free Radic Biol Med"xsd:string |
| http://purl.uniprot.org/citations/21320589 | http://purl.uniprot.org/core/pages | "1471-1479"xsd:string |
| http://purl.uniprot.org/citations/21320589 | http://purl.uniprot.org/core/title | "Redox activity of alpha-synuclein-Cu is silenced by Zn(7)-metallothionein-3."xsd:string |
| http://purl.uniprot.org/citations/21320589 | http://purl.uniprot.org/core/volume | "50"xsd:string |
| http://purl.uniprot.org/citations/21320589 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21320589 |
| http://purl.uniprot.org/citations/21320589 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/21320589 |
| http://purl.uniprot.org/uniprot/P25713#attribution-2285B7B1B103C7EEBBB3C4EBEF449352 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/21320589 |
| http://purl.uniprot.org/uniprot/P37840#attribution-0FBC7D007C8205F73F759DF78B80C45A | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/21320589 |
| http://purl.uniprot.org/uniprot/P37840#attribution-2285B7B1B103C7EEBBB3C4EBEF449352 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/21320589 |
| http://purl.uniprot.org/uniprot/#_P25713-mappedCitation-21320589 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21320589 |
| http://purl.uniprot.org/uniprot/P25713 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/21320589 |