Dual activity of PNGM-1 pinpoints the evolutionary origin of subclass B3 metallo-β-lactamases: a molecular and evolutionary study. Issue 1 (1st January 2019)

• Record Type: Journal Article
• Authors: Lee, Jung Hun; Takahashi, Masayuki; Jeon, Jeong Ho; Kang, Lin-Woo; Seki, Mineaki; Park, Kwang Seung; Hong, Myoung-Ki; Park, Yoon Sik; Kim, Tae Yeong; Karim, Asad Mustafa; Lee, Jung-Hyun; Nashimoto, Masayuki; Lee, Sang Hee
• Is Part Of: Emerging microbes & infections. Volume 8:Issue 1(2019)
• Page Start: 1688
• Page End: 1700
• Publication Date: 2019-01-01
• Subjects: Antimicrobial resistance -- subclass B3 metallo-β-lactamase -- tRNase Z -- dual activity -- structure and evolutionary origin; Medical microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.9041
• DOI: 10.1080/22221751.2019.1692638
• Languages: English
• ISSNs: 2222-1751

Abstract

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.