Discovery of antagonist peptides against bacterial helicase-primase interaction in B. stearothermophilus by reverse yeast three-hybrid

Gardiner, Laurence; Coyle, Barry J.; Chan, Weng C.; Soultanas, Panos

Abstract

Developing small-molecule antagonists against protein-protein interactions will provide powerful tools for mechanistic/functional studies and the discovery of new antibacterials. We have developed a reverse yeast three-hybrid approach that allows high-throughput screening for antagonist peptides against essential protein-protein interactions. We have applied our methodology to the essential bacterial helicase-primase interaction in Bacillus stearothermophilus and isolated a unique antagonist peptide. This peptide binds to the primase, thus excluding the helicase and inhibiting an essential interaction in bacterial DNA replication. We provide proof of principle that our reverse yeast three-hybrid method is a powerful "one-step" screen tool for direct high-throughput antagonist peptide selection against any protein-protein interaction detectable by traditional yeast two-hybrid systems. Such peptides will provide useful "leads" for the development of new antibacterials. ©2005 Elsevier Ltd All rights reserved.

Citation

Gardiner, L., Coyle, B. J., Chan, W. C., & Soultanas, P. (2005). Discovery of antagonist peptides against bacterial helicase-primase interaction in B. stearothermophilus by reverse yeast three-hybrid. Cell Chemistry Biology, 12(5), 595-604. https://doi.org/10.1016/j.chembiol.2005.04.007

• Journal Article Type: Article
• Acceptance Date: Apr 4, 2005
• Online Publication Date: May 20, 2005
• Publication Date: 2005-05
• Deposit Date: May 12, 2023
• Journal: Chemistry and Biology
• Print ISSN: 1074-5521
• Publisher: Cell Press
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 5
• Pages: 595-604
• DOI: https://doi.org/10.1016/j.chembiol.2005.04.007
• Public URL: https://nottingham-repository.worktribe.com/output/3137745
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S1074552105001018