6LI4

Crystal structure of MCR-1-S

6LI4 の概要

• エントリーDOI: 10.2210/pdb6li4/pdb
• 分子名称: Probable phosphatidylethanolamine transferase Mcr-1, ZINC ION (3 entities in total)
• 機能のキーワード: mcr-1 zn(ii), antibiotic, transferase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 74593.76

構造登録者

Zhang, Q.,Wang, M.,Sun, H. (登録日: 2019-12-10, 公開日: 2020-09-16, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.78 Å)