6LI4

Crystal structure of MCR-1-S

Summary for 6LI4

• Entry DOI: 10.2210/pdb6li4/pdb
• Descriptor: Probable phosphatidylethanolamine transferase Mcr-1, ZINC ION (3 entities in total)
• Functional Keywords: mcr-1 zn(ii), antibiotic, transferase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 74593.76

Authors

Zhang, Q.,Wang, M.,Sun, H. (deposition date: 2019-12-10, release date: 2020-09-16, Last modification date: 2024-10-30)

Primary citation

Sun, H.,Zhang, Q.,Wang, R.,Wang, H.,Wong, Y.T.,Wang, M.,Hao, Q.,Yan, A.,Kao, R.Y.,Ho, P.L.,Li, H.
Resensitizing carbapenem- and colistin-resistant bacteria to antibiotics using auranofin.
Nat Commun, 11:5263-5263, 2020

PubMed Abstract: Global emergence of Gram-negative bacteria carrying the plasmid-borne resistance genes, bla and mcr, raises a significant challenge to the treatment of life-threatening infections by the antibiotics, carbapenem and colistin (COL). Here, we identify an antirheumatic drug, auranofin (AUR) as a dual inhibitor of metallo-β-lactamases (MBLs) and mobilized colistin resistance (MCRs), two resistance enzymes that have distinct structures and substrates. We demonstrate that AUR irreversibly abrogates both enzyme activity via the displacement of Zn(II) cofactors from their active sites. We further show that AUR synergizes with antibiotics on killing a broad spectrum of carbapenem and/or COL resistant bacterial strains, and slows down the development of β-lactam and COL resistance. Combination of AUR and COL rescues all mice infected by Escherichia coli co-expressing MCR-1 and New Delhi metallo-β-lactamase 5 (NDM-5). Our findings provide potential therapeutic strategy to combine AUR with antibiotics for combating superbugs co-producing MBLs and MCRs.

PubMed: 33067430
DOI: 10.1038/s41467-020-18939-y

Experimental method

X-RAY DIFFRACTION (1.78 Å)