RRC ID 46980
Author Ueno K, Tamura Y, Chibana H.
Title 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.
Journal Yeast
Abstract 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.
Volume 27(7)
Pages 369-78
Published 2010-7-1
DOI 10.1002/yea.1759
PMID 20148388
MeSH Antifungal Agents / metabolism Antifungal Agents / pharmacology* Candida glabrata / drug effects* Candida glabrata / genetics Candida glabrata / growth & development Computer Simulation Designer Drugs / metabolism Designer Drugs / pharmacology* Drug Design* Enzyme-Linked Immunosorbent Assay Gene Knockdown Techniques Humans Peptides / metabolism Peptides / pharmacology* Profilins / antagonists & inhibitors* Profilins / metabolism Protein Binding
IF 3.143
Times Cited 1
WOS Category BIOTECHNOLOGY & APPLIED MICROBIOLOGY MYCOLOGY MICROBIOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Pathogenic microorganisms ?