Abstract
TIR1 is F-Box protein, a component of an SCF-class E3 ubiquitin-ligase and was identified as auxin receptor. Arabdidopsis plants have five redundant auxin receptors, AFBs homologous to TIR1. We recently developed alpha-alkyl-auxin as a novel anti-auxin probe specifically binding to TIR1/AFB auxin receptor. X-ray crystal structural analysis of TIR1-anti auxin probes demonstrates its binding mode and inhibitory mechanism. On basis on crystal structures, we rationally designed various new auxin probes to have high affinity to TIR1 utilizing structure-based drug design (SBDD) approach. We also searched TIR1 binding ligands from small molecule databases by in silico screening method. As the results of SBDD and virtual screening approach, we identified some candidates of TIR1-specific probes exhibiting high inhibitory activity on SCF-TIR1 signaling. Our new TIR1/AFB specific anti auxin can be powerful tools for auxin biology.
