In silico identification and in vitro evaluation of a protein-protein interaction inhibitor of Escherichia coli fatty acid biosynthesis.

Abstract

To combat the rise in antibiotic resistance, new targets must be identified and probes against them developed. Protein-protein interactions (PPI) of bacterial type II fatty acid biosynthesis (FAS-II) represent an untapped, yet rich area for new antibiotic discovery. Here, we present a computational and in vitro workflow for the discovery of new inhibitors of PPI in Escherichia coli FAS-II. As part of this study, we identified suramin, an existing treatment for African sleeping sickness, to effectively block the interaction of E. coli dehydratase FabA and the acyl carrier protein EcACP, with an IC50 = 85 μΜ. This finding validates a workflow that combines in silico screening with in vitro PPI assays to identify probes appropriate for further optimization.

• Authors: Katherine Charov, Michael D Burkart
• Journal: Chemical biology & drug design (Chem Biol Drug Des) Vol. 98 Issue 1 Pg. 94-101 (07 2021) ISSN: 1747-0285 [Electronic] England
• PMID: 33905605 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2021 John Wiley & Sons A/S.

Chemical References

• Acyl Carrier Protein
• Escherichia coli Proteins
• Fatty Acids
• Hydro-Lyases

Topics

• Acyl Carrier Protein (metabolism)
• Amino Acid Sequence
• Computer Simulation
• Escherichia coli (metabolism)
• Escherichia coli Proteins (metabolism)
• Fatty Acids (biosynthesis)
• Hydro-Lyases (metabolism)
• In Vitro Techniques
• Protein Binding
• Protein Conformation