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A Single Tool to Monitor Multiple Protein-Protein Interactions of the Escherichia coli Acyl Carrier Protein.

Abstract

Protein-protein interactions are ubiquitous to all domains of life and have gained recent interest as drug targets. However, many current methods to study protein-protein interactions can be costly and are low-throughput. Here, we demonstrate a solvatochromic tool based on the natural post-translational modification of the Escherichia coli acyl carrier protein (EcACP) used to visualize protein-protein interactions between EcACP and 13 different partner enzymes from several biosynthetic pathways. We use this tool to confirm proposed interactions between EcACP and both catalytic and regulatory proteins. We also show the utility of this method toward detecting allosteric changes to partner enzyme structure and the validation of active site inhibitors. We anticipate the future adaptation of this assay into a high-throughput screen for antibiotic discovery.

Authors+Show Affiliations

Department of Chemistry and Biochemistry , University of California, San Diego , 9500 Gilman Drive , La Jolla , California 92093-0358 , United States.Department of Chemistry and Biochemistry , University of California, San Diego , 9500 Gilman Drive , La Jolla , California 92093-0358 , United States.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31317739

Citation

Charov, Katherine, and Michael D. Burkart. "A Single Tool to Monitor Multiple Protein-Protein Interactions of the Escherichia Coli Acyl Carrier Protein." ACS Infectious Diseases, 2019.
Charov K, Burkart MD. A Single Tool to Monitor Multiple Protein-Protein Interactions of the Escherichia coli Acyl Carrier Protein. ACS Infect Dis. 2019.
Charov, K., & Burkart, M. D. (2019). A Single Tool to Monitor Multiple Protein-Protein Interactions of the Escherichia coli Acyl Carrier Protein. ACS Infectious Diseases, doi:10.1021/acsinfecdis.9b00150.
Charov K, Burkart MD. A Single Tool to Monitor Multiple Protein-Protein Interactions of the Escherichia Coli Acyl Carrier Protein. ACS Infect Dis. 2019 Jul 30; PubMed PMID: 31317739.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Single Tool to Monitor Multiple Protein-Protein Interactions of the Escherichia coli Acyl Carrier Protein. AU - Charov,Katherine, AU - Burkart,Michael D, Y1 - 2019/07/30/ PY - 2019/7/19/pubmed PY - 2019/7/19/medline PY - 2019/7/19/entrez KW - acyl carrier protein interactome KW - fatty acid biosynthesis KW - in vitro drug screening KW - protein−protein interactions KW - solvatochromism JF - ACS infectious diseases JO - ACS Infect Dis N2 - Protein-protein interactions are ubiquitous to all domains of life and have gained recent interest as drug targets. However, many current methods to study protein-protein interactions can be costly and are low-throughput. Here, we demonstrate a solvatochromic tool based on the natural post-translational modification of the Escherichia coli acyl carrier protein (EcACP) used to visualize protein-protein interactions between EcACP and 13 different partner enzymes from several biosynthetic pathways. We use this tool to confirm proposed interactions between EcACP and both catalytic and regulatory proteins. We also show the utility of this method toward detecting allosteric changes to partner enzyme structure and the validation of active site inhibitors. We anticipate the future adaptation of this assay into a high-throughput screen for antibiotic discovery. SN - 2373-8227 UR - https://www.unboundmedicine.com/medline/citation/31317739/A_single_tool_to_monitor_multiple_protein-protein_interactions_of_the_Escherichia_coli_acyl_carrier_protein L2 - https://dx.doi.org/10.1021/acsinfecdis.9b00150 DB - PRIME DP - Unbound Medicine ER -