Identification of Ustilago maydis Aurora Kinase As a Novel Antifungal Target

Infestation of crops by pathogenic fungi has continued to have a major impact by reducing yield and quality, emphasizing the need to identify new targets and develop new agents to improve methods of crop protection. Here we present Aurora kinase from the phytopathogenic fungus Ustilago maydis as a n...

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Veröffentlicht in:ACS chemical biology 2011-09, Vol.6 (9), p.926-933
Hauptverfasser: Tückmantel, Sandra, Greul, Jörg N, Janning, Petra, Brockmeyer, Andreas, Grütter, Christian, Simard, Jeffrey R, Gutbrod, Oliver, Beck, Michael E, Tietjen, Klaus, Rauh, Daniel, Schreier, Peter H
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Sprache:eng
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Zusammenfassung:Infestation of crops by pathogenic fungi has continued to have a major impact by reducing yield and quality, emphasizing the need to identify new targets and develop new agents to improve methods of crop protection. Here we present Aurora kinase from the phytopathogenic fungus Ustilago maydis as a novel target for N-substituted diaminopyrimidines, a class of small-molecule kinase inhibitors. We show that Aurora kinase is essential in U. maydis and that diaminopyrimidines inhibit its activity in vitro. Furthermore, we observed an overall good correlation between in vitro inhibition of Aurora kinase and growth inhibition of diverse fungi in vivo. In vitro inhibition assays with Ustilago and human Aurora kinases indicate that some compounds of the N-substituted diaminopyrimidine class show specificity for the Ustilago enzyme, thus revealing their potential as selective fungicides.
ISSN:1554-8929
1554-8937
DOI:10.1021/cb200112y