Resumo

Approximately one third of all proteins have been estimated to contain at least one metal cofactor, being named metalloproteins. These represent one of the most diverse classes of proteins, containing metal ions that bind to specific sites, providing catalytic, regulatory and structural functions. Bioinformatic tools have been developed to predict metalloproteins encoded by an organism based only on its genome sequence. Its function as well as the type of metal binder can also be predict by bioinformatics approach. Paracoccidioides complex includes termodimorphic pathogenic fungi that are found as saprobic mycelia in the environment and as yeast, the parasitic form, in host tissues. They are the etiologic agents of Paracoccidioidomycosis, a prevalent systemic mycosis in Latin America, with high incidence in Brazil. It is known that many metalloproteins are important for virulence of several pathogenic microorganisms. On this way, the present work aimed to predict the cooper, iron and zinc proteins encoded by the genomes of three phylogenetic species of Paracoccidioides spp. (Pb01, Pb03 and Pb18). The metalloproteins were identified using bioinformatics approaches based on structure, annotation and domains. Some metalloproteins, which were predict to have two metal ligands have undergone by three-dimensional structure analysis. Cu-, Fe- and Zn-proteins represents 7% of the total proteins encoded by Paracoccidioides spp genomes. Zinc-proteins were the most abundant metalloproteins representing 5.7% of the fungus proteome, while copper and iron proteins represent 0.3% and 1.2% respectively. Functional classification revealed that metalloproteins are related to many cellular processes and the cellular localization showed that these proteins is spread all over the cell. Among the phylogenetic species, Pb01 had a greater number of exclusive proteins (54), followed by Pb03 and Pb18 who had the same number (28). In addition, we performed a SEC-ICPMS analysis of mycelium and yeast protein extracs in order to compare the metalloprotein profiles of the phases. Many of the identified metalloproteins had been described as virulence factors in other pathogens. The study of Paracoccidioides Cu-, Fe- and Zn- proteins bring to light new insights of the metal homeostasis of this pathogen, which is important for the understanding of fungal biology and virulence.