Cheickna Cissé
Structural study of anti-FUR peptide aptamers and their interactions with their target
Published on 19 January 2012
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Thesis presented January 19, 2012
Abstract:
FUR (Ferric Uptake Regulator) is a transcriptional regulator involved in the control of iron homeostasis. Specific to bacteria, FUR is an attractive antibacterial target. Before my arrival in the laboratory, four inhibitors interacting specifically with FUR had been isolated. The active part of these inhibitors consists of peptides of 13 amino acids. In this thesis I have used both theoretical and experimental approaches to study interactions of these peptides with FUR in order to understand the inhibition mechanism. I have synthesized several peptide sequences, shown through biochemical assays that some of them could inhibit FUR and I have identified residues important to the inhibitory activity. I have obtained theoretical models of FUR/peptide complexes consistent with experimental results, which reveal an inhibition pocket in FUR. Small molecules have then been selected though
in silico screening of this pocket, that could potentially inhibit FUR, and thus be interesting for therapeutic applications.
Keywords:
FUR, peptide aptamers, Molecular docking, DNA binding assays, AUTODOCK4, CHARMM
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