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7083945 
Journal Article 
From Peptide Aptamers to Inhibitors of FUR, Bacterial Transcriptional Regulator of Iron Homeostasis and Virulence 
Mathieu, S; Coves, J; Crouzy, S; Michaud-Soret, I; Cisse, C; Vitale, S; Ahmadova, A; Degardin, M; Perard, J; Colas, P; Miras, R; Boturyn, D; , 
2016 
Yes 
ACS Chemical Biology
ISSN: 1554-8929
EISSN: 1554-8937 
AMER CHEMICAL SOC 
WASHINGTON 
11 
9 
2519-2528 
English 
27409249 
WOS:000383639800016 
FUR (Ferric Uptake Regulator) protein is a global transcriptional regulator that senses iron status and controls the expression of genes involved in iron homeostasis, virulence, and oxidative stress. Ubiquitous in. Gram-negative bacteria and absent in eukaryotes, FUR is an attractive antivirulence target since the inactivation of the fur gene in various pathogens attenuates their virulence. The characterization of 13-aa-long anti-FUR linear peptides derived from the variable part of the anti-FUR peptide aptamers, that were previously shown to decrease pathogenic E. coli strain virulence in a fly infection model, is described herein. Modeling, docking, and experimental approaches in vitro (activity and interaction assays, mutations) and in cells (yeast two-hybrid assays) were combined to characterize the interactions of the peptides with FUR, and to understand their mechanism of inhibition. As a result, reliable structure models of two peptide FUR complexes are given. Inhibition sites are mapped in the groove between the two FUR subunits where DNA should also bind. Another peptide behaves differently and interferes with the dimerization itself. These results define these novel small peptide inhibitors as lead compounds for inhibition of the FUR transcription factor.