Interactions of the intact FsrC membrane histidine kinase with the tricyclic peptideinhibitor siamycin I revealed through synchrotron radiation circular dichroism

Abstract

The suitability of synchrotron radiation circular dichroism spectroscopy (SRCD) for studying interactions between the tricyclic peptide inhibitor siamycin I and the intact FsrC membrane sensor kinase in detergent micelles has been established. In the present study, tertiary structural changes demonstrate that inhibitor binding occurs at a different, non-overlapping site to the native ligand, GBAP.

Characterisation of Conformational and Ligand Binding Properties of Membrane Proteins Using Synchrotron Radiation Circular Dichroism (SRCD)

“…Qualitative studies showed that the affinity of the ligand GBAP to FsrC was 2 μM, monitored at a single wavelength of 277 nm. Further competitive binding studies with another ligand, siamycin I, showed that siamycin I did not compete with GBAP and that aromatic side-chain residues should be involved in the interaction with the ligand (Patching et al 2012 ; Phillips-Jones et al 2013 ).

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Narrow-spectrum inhibitors targeting an alternative menaquinone biosynthetic pathway of Helicobacter pylori

“…Siamycin I has been shown to directly inhibit the autophosphorylation activity of the FsrC quorum sensor of Enterococcus faecalis [42]. Synchrotron radiation circular spectroscopy revealed that the binding of siamycin I to FsrC exerts a significant effect on the local tertiary structures of the TyR and Trp resides of the protein and/or peptide ligands (gelatinase biosynthesis-activating pheromone) and siamycin I [43]. In this study, siamycin I was able to reduce the H. pylori colonization when administered at a daily dose that was 1/40 of the doses of EPA and DHA (Fig.…”

Advances in Microbiology, Infectious Diseases and Public Health

“…Siamycin inhibited QS-induced gelatinase production at 10 nM but it did not affect bacteria growth. It was also demonstrated that siamycin inhibited autophosphorylation of the histidine receptor kinase, FsrC (Ma et al 2011;Phillips-Jones et al 2013). It was also demonstrated that siamycin inhibited autophosphorylation of the histidine receptor kinase, FsrC (Ma et al 2011;Phillips-Jones et al 2013).…”