Interaction of isocitrate lyase with proteins involved in the energetic metabolism in Paracoccidioides lutzii
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2020
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Resumo
Background: Systemic mycosis is a cause of death of immunocompromised subjects.
The treatment directed to evade fungal pathogens shows severe limitations, such as time of drug
exposure and side effects. The paracoccidioidomycosis (PCM) treatment depends on the severity
of the infection and may last from months to years. Methods: To analyze the main interactions
of Paracoccidioides lutzii isocitrate lyase (ICL) regarding the energetic metabolism through affinity
chromatography, we performed blue native PAGE and co-immunoprecipitation to identify ICL
interactions. We also performed in silico analysis by homology, docking, hot-spot prediction and
contact preference analysis to identify the conformation of ICL complexes. Results: ICL interacted with
18 proteins in mycelium, 19 in mycelium-to-yeast transition, and 70 in yeast cells. Thirty complexes
were predicted through docking and contact preference analysis. ICL has seven main regions of
interaction with protein partners. Conclusions: ICL seems to interfere with energetic metabolism of
P. lutzii, regulating aerobic and anaerobic metabolism as it interacts with proteins from glycolysis,
gluconeogenesis, TCA and methylcitrate cycles, mainly through seven hot-spot residues.
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Protein–protein interaction, Paracoccidioides, Central metabolism, Isocitrate lyase
Citação
SILVA, Kleber Santiago Freitas e et al. Interaction of isocitrate lyase with proteins involved in the energetic metabolism in Paracoccidioides lutzii. Journal of Fungi, Basel, v. 6, n. 4, e309, 2020. DOI: 10.3390/jof6040309. Disponível em: https://www.mdpi.com/2309-608X/6/4/309. Acesso em: 22 nov. 2024.