Reference - Detail
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 |