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Deficits in Complex I enzymatic activity and an increase in oxidative damage have been identified in multiple brain regions of PD patients. Unravelling how PINK1 activity regulates mitochondria fate is pivotal. In the present study we characterized how human PD-related PINK1 mutants affect major PINK1 functions. Using molecular dynamics, we gain mechanistic insight into how specific mutations alter the tertiary structure and stability of PINK1\u2019s ATP-binding pocket, leading to an increased rigidity and stability. More importantly, we report a structural explanation for the enhanced kinase function of the PINK1-G411S mutant.<\/jats:p>","DOI":"10.1101\/2024.06.28.601304","type":"posted-content","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T04:25:14Z","timestamp":1719807914000},"source":"Crossref","is-referenced-by-count":0,"title":["PINK1-G411S mutant increases kinase stability and enhances mitochondrial-linked functions"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8863-1912","authenticated-orcid":false,"given":"Filipa B.","family":"Gon\u00e7alves","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8072-8557","authenticated-orcid":false,"given":"Francisco J.","family":"Enguita","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0830-0548","authenticated-orcid":false,"given":"Vanessa A.","family":"Morais","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"key":"2024070214151034000_2024.06.28.601304v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(06)70471-9"},{"key":"2024070214151034000_2024.06.28.601304v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-0186(01)00124-3"},{"key":"2024070214151034000_2024.06.28.601304v1.3","doi-asserted-by":"publisher","DOI":"10.1126\/science.1096284"},{"issue":"1993","key":"2024070214151034000_2024.06.28.601304v1.4","first-page":"166","article-title":"Mutations in the parkin gene cause autossomal recessive juvenile parkinsonism","volume":"169","year":"1998","journal-title":"Nat. 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