7YJS

Crystal structure of MCR-1-S treated by sodium aurothiosulfate

Summary for 7YJS

• Entry DOI: 10.2210/pdb7yjs/pdb
• Descriptor: Probable phosphatidylethanolamine transferase Mcr-1, GOLD ION (3 entities in total)
• Functional Keywords: mcr-1-s, antibiotic, sodium aurothiosulfate, transferase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 74856.88

Authors

Zhang, Q.,Sun, H.,Wang, M. (deposition date: 2022-07-20, release date: 2023-02-01, Last modification date: 2024-10-16)

Primary citation

Zhang, Q.,Wang, M.,Hu, X.,Yan, A.,Ho, P.L.,Li, H.,Sun, H.
Gold drugs as colistin adjuvants in the fight against MCR-1 producing bacteria.
J.Biol.Inorg.Chem., 28:225-234, 2023

PubMed Abstract: The emergence and rapid spread of the mobile colistin resistance gene mcr-1 among bacterial species and hosts significantly challenge the efficacy of "last-line" antibiotic colistin. Previously, we reported silver nitrate and auranofin serve as colistin adjuvants for combating mcr-1-positive bacteria. Herein, we uncovered more gold-based drugs and nanoparticles, and found that they exhibited varying degree of synergisms with colistin on killing mcr-1-positive bacteria. However, pre-activation of the drugs by either glutathione or N-acetyl cysteine, thus releasing and accumulating gold ions, is perquisite for their abilities to substitute zinc cofactor from MCR-1 enzyme. X-ray crystallography and biophysical studies further supported the proposed mechanism. This study not only provides basis for combining gold-based drugs and colistin for combating mcr-1-positive bacterial infections, but also undoubtedly opens a new horizon for metabolism details of gold-based drugs in overcoming antimicrobial resistance.

PubMed: 36662362
DOI: 10.1007/s00775-022-01983-y

Experimental method

X-RAY DIFFRACTION (2.5 Å)