Evolutionary relationships among protein lysine deacetylases of parasites causing neglected diseases

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases
Larissa L S ScholteLaila A Nahum

Abstract

The availability of the genomic data of diverse parasites provides an opportunity to identify new drug candidates against neglected tropical diseases affecting people worldwide. Histone modifying enzymes (HMEs) are potential candidates since they play key roles in the regulation of chromatin modifications, thus globally regulating gene expression. Furthermore, aberrant epigenetic states are often associated with human diseases, leading to great interest in HMEs as therapeutic targets. Our work focused on two families of protein lysine deacetylases (HDACs and sirtuins). First, we identified potential homologues in the predicted proteomes of selected taxa by using hidden Markov model profiles. Then, we reconstructed the evolutionary relationships of protein sequences by Bayesian inference and maximum likelihood method. In addition, we constructed homology models for five parasite HDACs to provide information for experimental validation and structure-based optimization of inhibitors. Our results showed that parasite genomes code for diverse HDACs and sirtuins. The evolutionary pattern of protein deacetylases with additional experimental data points to these enzymes as common drug targets among parasites. This work has improved the...Continue Reading

Citations

Nov 21, 2017·PLoS Neglected Tropical Diseases·Stéphanie CabyEmmanuel Roger
Jun 14, 2020·International Journal of Molecular Sciences·Balázs Zoltán Zsidó, Csaba Hetényi
May 2, 2018·Frontiers in Medicine·Larissa L S ScholteLaila A Nahum
Mar 4, 2021·PLoS Neglected Tropical Diseases·Hugo Rolando VacaMara Cecilia Rosenzvit

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