Dual activity of PNGM-1 pinpoints the evolutionary origin of subclass B3 metallo-β-lactamases: a molecular and evolutionary study
| العنوان: | Dual activity of PNGM-1 pinpoints the evolutionary origin of subclass B3 metallo-β-lactamases: a molecular and evolutionary study |
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| المؤلفون: | Kwang Seung Park, Mineaki Seki, Jung Hun Lee, Masayuki Takahashi, Lin-Woo Kang, Jeong Ho Jeon, Yoon Sik Park, Tae Yeong Kim, Sang Hee Lee, Myoung Ki Hong, Masayuki Nashimoto, Jung-Hyun Lee, Asad Mustafa Karim |
| المساهمون: | Myongji University, Niigata University of Pharmacy and Applied Life Sciences, Konkuk University [Seoul], Marine Biotechnology Research Center, Korea Institute of Ocean Science and Technology (KIOST), This work was supported by research grants from the Bio & Medical Technology Development Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (MSIT, grants NRF-2017M3A9E4078014 and NRF-2017R1A2B4002315 to S.H.L., NRF-2017M3A9E4078017 to L.-W.K., and NRF-2019R1C1C1008615 to J.H.L.), the Korea Centers for Disease Control and Prevention (grant 2017ER540402 to S.H.L.), and the Takeda Science Foundation to M.T., We thank our colleagues, both past and present, at the National Leading Research Laboratory of Drug Resistance Proteomics, Myongji University, for sharing their insights into the concepts presented here, S.G. Kang and B.C. Jeong for early support of this work, and J.H. Kim and S.K. Malik for helpful discussions. J.H.L., J.H.J., and J.-H.L. identified and prepared a novel MBL gene and protein. J.H.L., M.T., M.N., K.S.P., and M.S. performed a genetic and functional analysis. J.H.J., T.Y.K., and A.M.K. conducted the mutant analysis. L.-W.K., M.-K.H., and Y.S.P. carried out the crystal structure studies and data analysis. S.H.L. and M.N. analyzed the evolutionary origin. |
| المصدر: | Emerging microbes & infections Emerging microbes & infections, Earliest : Springer-Nature ; Latest : Taylor & Francis, 2019, 8 (1), pp.1688-1700. ⟨10.1080/22221751.2019.1692638⟩ |
| بيانات النشر: | Informa UK Limited, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, Epidemiology, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030106 microbiology, Immunology, Biology, Antimicrobial resistance, Microbiology, Subclass, Metallo β lactamase, dual activity, 03 medical and health sciences, Antibiotic resistance, Phylogenetics, Virology, Molecular genetics, Drug Discovery, medicine, tRNase Z, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, Antiinfective agent, Phylogenetic tree, General Medicine, bacterial infections and mycoses, 030104 developmental biology, Infectious Diseases, structure and evolutionary origin, Beta-lactamase, Parasitology, subclass B3 metallo-β-lactamase |
| الوصف: | International audience; 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. |
| تدمد: | 2222-1751 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::235960e93d656de612f56af86dc8c37cTest https://doi.org/10.1080/22221751.2019.1692638Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....235960e93d656de612f56af86dc8c37c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22221751 |
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