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Phylogenetic and in silico structural analysis of the Parkinson disease-related kinase PINK1

✍ Scribed by Fernando Cardona; Jose Vicente Sánchez-Mut; Hernán Dopazo; Jordi Pérez-Tur

Publisher
John Wiley and Sons
Year
2011
Tongue
English
Weight
726 KB
Volume
32
Category
Article
ISSN
1059-7794

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✦ Synopsis

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.

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