Issue 30, 2019

Antimicrobial silver targets glyceraldehyde-3-phosphate dehydrogenase in glycolysis of E. coli

Abstract

Silver has long been used as an antibacterial agent, yet its molecular targets remain largely unknown. Using a custom-designed coupling of gel electrophoresis with inductively coupled plasma mass spectrometry (GE-ICP-MS), we identified six silver-binding proteins in E. coli. The majority of the identified proteins are associated with the central carbon metabolism of E. coli. Among them, we unveil that GAPDH, an essential enzyme in glycolysis, serves as a vital target of Ag+ in E. coli for the first time. We demonstrate that silver inhibits the enzymatic function of GAPDH through targeting Cys149 in its catalytic site. The X-ray structure reveals that Ag+ coordinates to Cys149 and His176 with a quasi-linear geometry (S–Ag–N angle of 157°). And unexpectedly, two Ag+ ions coordinate to Cys288 in the non-catalytic site with weak argentophilic interaction (Ag⋯Ag distance of 2.9 Å). This is the first report on antimicrobial Ag+ targeting a key enzyme in the glycolytic pathway of E. coli. The findings expand our knowledge on the mode of action and bio-coordination chemistry of silver, particularly silver-targeting residues in proteins at the atomic level.

Graphical abstract: Antimicrobial silver targets glyceraldehyde-3-phosphate dehydrogenase in glycolysis of E. coli

Supplementary files

Article information

Article type
Edge Article
Submitted
24 Apr 2019
Accepted
14 Jun 2019
First published
24 Jun 2019
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2019,10, 7193-7199

Antimicrobial silver targets glyceraldehyde-3-phosphate dehydrogenase in glycolysis of E. coli

H. Wang, M. Wang, X. Yang, X. Xu, Q. Hao, A. Yan, M. Hu, R. Lobinski, H. Li and H. Sun, Chem. Sci., 2019, 10, 7193 DOI: 10.1039/C9SC02032B

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