Emerging Microbes & Infections, 2019. 8(1), 1688-1700, DOI: https://doi.org/10.1080/22221751.2019.1692638

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

Jung Hun Lee, Masayuki Takahashib;Jeong Ho Jeona;Lin-Woo Kang;Mineaki Seki;Kwang Seung Park;Myoung-Ki Hong;Yoon Sik Park;Tae Yeong Kim;Asad Mustafa Karim;Jung-Hyun Lee;Masayuki Nashimoto;Sang Hee Lee

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.

• DOI: https://doi.org/10.1080/22221751.2019.1692638
• ISBN or ISSN: 2222-1751

• 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
• This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.