Next Article in Journal
Bacteriophage Interactions with Marine Pathogenic Vibrios: Implications for Phage Therapy
Next Article in Special Issue
The Macromolecular Machines that Duplicate the Escherichia coli Chromosome as Targets for Drug Discovery
Previous Article in Journal
Efficacy of an Optimised Bacteriophage Cocktail to Clear Clostridium difficile in a Batch Fermentation Model
Previous Article in Special Issue
Screening of E. coli β-clamp Inhibitors Revealed that Few Inhibit Helicobacter pylori More Effectively: Structural and Functional Characterization
Article Menu

Export Article

Open AccessArticle
Antibiotics 2018, 7(1), 14; https://doi.org/10.3390/antibiotics7010014

Fragment-Based Discovery of Inhibitors of the Bacterial DnaG-SSB Interaction

1
Molecular Horizons and School of Chemistry, University of Wollongong, and Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia
2
Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia
3
Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia
*
Author to whom correspondence should be addressed.
Received: 15 January 2018 / Revised: 9 February 2018 / Accepted: 13 February 2018 / Published: 22 February 2018
(This article belongs to the Special Issue Bacterial DNA Replication and Replication Inhibitors)
View Full-Text   |   Download PDF [6193 KB, uploaded 22 February 2018]   |  

Abstract

In bacteria, the DnaG primase is responsible for synthesis of short RNA primers used to initiate chain extension by replicative DNA polymerase(s) during chromosomal replication. Among the proteins with which Escherichia coli DnaG interacts is the single-stranded DNA-binding protein, SSB. The C-terminal hexapeptide motif of SSB (DDDIPF; SSB-Ct) is highly conserved and is known to engage in essential interactions with many proteins in nucleic acid metabolism, including primase. Here, fragment-based screening by saturation-transfer difference nuclear magnetic resonance (STD-NMR) and surface plasmon resonance assays identified inhibitors of the primase/SSB-Ct interaction. Hits were shown to bind to the SSB-Ct-binding site using 15N–1H HSQC spectra. STD-NMR was used to demonstrate binding of one hit to other SSB-Ct binding partners, confirming the possibility of simultaneous inhibition of multiple protein/SSB interactions. The fragment molecules represent promising scaffolds on which to build to discover new antibacterial compounds. View Full-Text
Keywords: antibacterial agents; fragment-based screening; primase; protein–protein interactions; SSB antibacterial agents; fragment-based screening; primase; protein–protein interactions; SSB
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Share & Cite This Article

MDPI and ACS Style

Chilingaryan, Z.; Headey, S.J.; Lo, A.T.Y.; Xu, Z.-Q.; Otting, G.; Dixon, N.E.; Scanlon, M.J.; Oakley, A.J. Fragment-Based Discovery of Inhibitors of the Bacterial DnaG-SSB Interaction. Antibiotics 2018, 7, 14.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Antibiotics EISSN 2079-6382 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top