Inhibiting Fungal Multidrug Resistance by Disrupting an Activator-Mediator Interaction With the Small Molecule iKIX1

ABSTRACT: Eukaryotic transcription activators stimulate the expression of specific sets of target genes through recruitment of co-activators such as the RNA polymerase II-interacting Mediator complex. We previously identified an activator-targeted ~85 amino acid three-helix bundle KIX domain in the human MED15 Mediator subunit that is structurally conserved in Gal11 Mediator subunits in fungi. The Gal11 KIX domain is engaged by pleiotropic drug resistance transcription factor (Pdr1) orthologues, key regulators of the multidrug resistance (MDR) pathway in S. cerevisiae and in the clinically important human pathogen Candida glabrata. Drug-resistant clinical isolates of C. glabrata most commonly harbour point mutations in Pdr1 that render it constitutively active, suggesting that this transcriptional a

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Joy Nishikawa 

PROVIDER: E-GEOD-74361 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress