1. Conservation of Cdc14 phosphatase specificity in plant fungal pathogens: implications for antifungal development.
- Author
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DeMarco AG, Milholland KL, Pendleton AL, Whitney JJ, Zhu P, Wesenberg DT, Nambiar M, Pepe A, Paula S, Chmielewski J, Wisecaver JH, Tao WA, and Hall MC
- Subjects
- Amino Acid Sequence, Fungi, Molecular Docking Simulation, Molecular Dynamics Simulation, Phylogeny, Plants classification, Plants genetics, Plants microbiology, Protein Binding, Protein Interaction Domains and Motifs, Protein Tyrosine Phosphatases chemistry, Protein Tyrosine Phosphatases genetics, Structure-Activity Relationship, Substrate Specificity, Biological Evolution, Disease Resistance, Host-Pathogen Interactions, Plants enzymology, Protein Tyrosine Phosphatases metabolism
- Abstract
Cdc14 protein phosphatases play an important role in plant infection by several fungal pathogens. This and other properties of Cdc14 enzymes make them an intriguing target for development of new antifungal crop treatments. Active site architecture and substrate specificity of Cdc14 from the model fungus Saccharomyces cerevisiae (ScCdc14) are well-defined and unique among characterized phosphatases. Cdc14 appears absent from some model plants. However, the extent of conservation of Cdc14 sequence, structure, and specificity in fungal plant pathogens is unknown. We addressed this by performing a comprehensive phylogenetic analysis of the Cdc14 family and comparing the conservation of active site structure and specificity among a sampling of plant pathogen Cdc14 homologs. We show that Cdc14 was lost in the common ancestor of angiosperm plants but is ubiquitous in ascomycete and basidiomycete fungi. The unique substrate specificity of ScCdc14 was invariant in homologs from eight diverse species of dikarya, suggesting it is conserved across the lineage. A synthetic substrate mimetic inhibited diverse fungal Cdc14 homologs with similar low µM K
i values, but had little effect on related phosphatases. Our results justify future exploration of Cdc14 as a broad spectrum antifungal target for plant protection.- Published
- 2020
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