Dual activity of PNGM-1 pinpoints the evolutionary origin of subclass B3 metallo-β-lactamases: a molecular and evolutionary study
| Autor: | Jung Hun Lee, Masayuki Takahashi, Jeong Ho Jeon, 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 |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Emerging Microbes and Infections, Vol 8, Iss 1, Pp 1688-1700 (2019) |
| Druh dokumentu: | article |
| ISSN: | 22221751 2222-1751 |
| DOI: | 10.1080/22221751.2019.1692638 |
| Popis: | ABSTRACTResistance 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. |
| Databáze: | Directory of Open Access Journals |
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