title: Phylogenetic and in silico structural analysis of the Parkinson disease-related kinase PINK1.
abstract: Parkinson disease (PD) is the second most common neurodegenerative disorder and is characterized by the loss of dopaminergic neurons in the substantia nigra. Mutations in PINK1 were shown to cause recessive familial PD, and today are proposed to be associated with the disease via mitochondrial dysfunction and oxidative damage. The PINK1 gene comprises eight exons, which encode a ubiquitously expressed 581 amino acid protein that contains an N-terminal mitochondrial targeting domain and a serine/threonine protein kinase. To better understand the relationship between PINK1 and PD we have first analyzed the evolutionary history of the gene showing its late emergence in evolution. In addition, we have modeled the three-dimensional structure of PINK1 and found some evidences that help to explain the effect of some PD-related mutations in this protein's function.
authors.affiliation: Unitat de Genètica Molecular, Institut de Biomedicina de València-CSIC, Valencia, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Cardona
authors.forename: Jose Vicente
authors.initials: JV
authors.lastname: Sánchez-Mut
authors.forename: Hernán
authors.initials: H
authors.lastname: Dopazo
authors.forename: Jordi
authors.initials: J
authors.lastname: Pérez-Tur
mesh_terms: D001483:Base Sequence; D006801:Humans; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000235:genetics*; D010802:Phylogeny; D011487:Protein Conformation; D011494:Protein Kinases / Q000235:genetics*; D016415:Sequence Alignment; D000099202:PTEN-Induced Putative Kinase
chemical_list: D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase