Dual activity of PNGM-1 pinpoints the evolutionary origin of subclass B3 metallo- β -lactamases: a molecular and evolutionary study - Institut Pasteur Access content directly
Journal Articles Emerging microbes & infections Year : 2019

Dual activity of PNGM-1 pinpoints the evolutionary origin of subclass B3 metallo- β -lactamases: a molecular and evolutionary study

Abstract

Resistance to β-lactams is one of the most serious problems associated with Gram-negative infections. β-Lactamases are able to hydrolyze β-lactams such as cephalosporins and/or carbapenems. Evolutionary origin of metallo-β-lactamases (MBLs), conferring critical antibiotic resistance threats, remains unknown. We discovered PNGM-1, the novel subclass B3 MBL, in deep-sea sediments that predate the antibiotic era. Here, our phylogenetic analysis suggests that PNGM-1 yields insights into the evolutionary origin of subclass B3 MBLs. We reveal the structural similarities between tRNase Zs and PNGM-1, and demonstrate that PNGM-1 has both MBL and tRNase Z activities, suggesting that PNGM-1 is thought to have evolved from a tRNase Z. We also show kinetic and structural comparisons between PNGM-1 and other proteins including subclass B3 MBLs and tRNase Zs. These comparisons revealed that the B3 MBL activity of PNGM-1 is a promiscuous activity and subclass B3 MBLs are thought to have evolved through PNGM-1 activity.
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pasteur-02399571 , version 1 (09-12-2019)

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Jung Hun Lee, Masayuki Takahashi, Jeong Ho Jeon, Lin-Woo Kang, Mineaki Seki, et al.. Dual activity of PNGM-1 pinpoints the evolutionary origin of subclass B3 metallo- β -lactamases: a molecular and evolutionary study. Emerging microbes & infections, 2019, 8 (1), pp.1688-1700. ⟨10.1080/22221751.2019.1692638⟩. ⟨pasteur-02399571⟩

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