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Yeast. 2010 Jul;27(7):369-78. doi: 10.1002/yea.1759.

Target validation and ligand development for a pathogenic fungal profilin, using a knock-down strain of pathogenic yeast Candida glabrata and structure-based ligand design.

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  • 1Medical Mycology Research Center (MMRC), Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8673, Japan. uenok5@restaff.chiba-u.jp


The emergence of antifungal drug resistance is triggering vigorous searches for novel antifungal targets and lead compounds. In this study, we focused on fungal profilin, which is a small actin control protein sharing limited homology to human profilin. To validate its potentiality as a target, a profilin-conditional mutant of the pathogenic yeast Candida glabrata was constructed, using a regulatable Tet promoter, and its growth was monitored in vitro. Repression of profilin expression led to severe growth defect, demonstrating the potential of this protein as a novel antifungal target. Next, novel peptides binding to the active interface of profilin were designed by computer simulation. ELISA analysis showed that these peptides did bind to the wild-type profilin but bound less strongly to a profilin with amino acid substitutions at the active interface. Hence, we show here that profilin is a potential antifungal target and offer novel peptide ligands.

Copyright (c) 2010 John Wiley & Sons, Ltd.

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