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

CARDONA F.; SÁNCHEZ-MUT J. V.; DOPAZO H.; J. PEREZ TUR

HUMAN MUTATION

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2011 vol. 32 p. 369 - 378

1059-7794

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 nowadays 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. 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