title: Identification of Ustilago maydis Aurora kinase as a novel antifungal target.
abstract: 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.
authors.affiliation: Chemical Genomics Centre of the Max Planck Society, Dortmund, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Tückmantel
authors.forename: Jörg N
authors.initials: JN
authors.lastname: Greul
authors.forename: Petra
authors.initials: P
authors.lastname: Janning
authors.forename: Andreas
authors.initials: A
authors.lastname: Brockmeyer
authors.forename: Christian
authors.initials: C
authors.lastname: Grütter
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Simard
authors.forename: Oliver
authors.initials: O
authors.lastname: Gutbrod
authors.forename: Michael E
authors.initials: ME
authors.lastname: Beck
authors.forename: Klaus
authors.initials: K
authors.lastname: Tietjen
authors.forename: Daniel
authors.initials: D
authors.lastname: Rauh
authors.forename: Peter H
authors.initials: PH
authors.lastname: Schreier
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D064127:Aurora Kinases; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014588:Ustilago / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases