PKA Subunits in the Human Pathogen Paracoccidioides: An in Silico Approach
Journal: International Journal of Biochemistry & Physiology (Vol.1, No. 1)Publication Date: 2016-06-21
Authors : Sestari SJ Brito WA Lacerda JGVC; Salem Izacc SM;
Page : 1-9
Keywords : PKA; Paracoccidioides; in silico;
Abstract
Paracoccidioides brasiliensis and P. lutzii is the causative agent of paracoccidioidomycosis, a primary systemic mycosis with different clinical manifestations. Infection occurs when hypha-fragments or spores are inhaled by the host, an event that induces Paracoccidioides cells to switch to the yeast form. The cAMP-PKA signaling pathway is important in controlling the morphological transition, as well as several development processes in fungal pathogens. PKA holoenzyme is an inactive tetramer composed of two regulatory and two catalytic subunits. When cAMP binds to the regulatory subunits, the catalytic subunits are released and become active. These active subunits subsequently phosphorylate protein kinases, transcription factors, and other substrates. In this study, we show an in silico characterization of the PKA subunits from three strains of Paracoccidioides. The genome of each strain encodes a single regulatory, PbPKA-R, and two catalytic subunits, PbPKA-C1 and PbPKA-C2. The subunits are highly conserved among the strains analyzed. The computer-based prediction suggests that PKA can be found in more than one subcellular location: PKA-R and PKA-C2 are mainly localized in the nucleus, whereas PKA-C1 seems to act predominantly in the cytosol. Each PKA-R subunit presents two tandem copies of the cyclic nucleotide monophosphate-binding (CNMP) domain at the C-terminus and each PKA-C has a protein kinase and an AGC-kinase C-terminal domain. Alignment of human and Paracoccidioides PKA subunits reveals a huge discrepancy in the N-terminal sequences of these two organisms. This sequence divergence between human and Paracoccidioides subunits combined with the pivotal role that PKA plays in many cellular processes, makes this protein an interesting target for antifungal drugs.
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