The 5´ → 3´ Exoribonuclease 2 as a Potential Target for Developing Fungicides to Control the Panama Disease

Abstract

An outbreak of Fusarium oxysporum f. sp. cubense Tropical Race 4 is currently threatening the global production of bananas. Due to the clonal nature of commercial banana plants, selecting resistant cultivars does not seem feasible; therefore, alternative approaches to crop protection must be developed. The 5´ → 3´ exoribonuclease XRN2/RAT1 is involved in 5´ → 3´ RNA decay. Fungal studies with XRN2 and conditional mutants have illustrated the crucial role of this enzyme, suggesting XRN2 should be considered as target to searching for novel inhibitors that might be used as fungicides to control Panama disease. Our in silico analysis of Tropical Race 4 XRN2 (FocTR4XRN2) revealed characteristic features of 5´ → 3´ exoribonuclease such as the catalytic domain that recognizes 5´-monophosphorylated RNA and catalyses the processed cleavage of mononucleotides. A delimited cavity showing the potential for substrate uptake appears prone to interacting with small molecules that might inhibit its activity. The catalytic domain in FocTR4XRN2 harbors a CCHC motif, which is conserved in orthologous proteins from filamentous fungi but lacking in yeasts. The residues involved in the interaction with the pyrophosphohydrolase RAI1 are also conserved. Molecular docking reveals the potential interaction of FocTR4XRN2 with the natural inhibitor adenosine 3´, 5´ bisphosphate, and suggests this approach is reliable to screen for novel enzyme inhibitors that could be help in suppressing the progression of causal agents of Panama disease.