دورية أكاديمية
N-Formimidoylation/-iminoacetylation modification in aminoglycosides requires FAD-dependent and ligand-protein NOS bridge dual chemistry
| العنوان: | N-Formimidoylation/-iminoacetylation modification in aminoglycosides requires FAD-dependent and ligand-protein NOS bridge dual chemistry |
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| المؤلفون: | Wang, Yung-Lin, Chang, Chin-Yuan, Hsu, Ning-Shian, Lo, I-Wen, Lin, Kuan-Hung, Chen, Chun-Liang, Chang, Chi-Fon, Wang, Zhe-Chong, Ogasawara, Yasushi, Dairi, Tohru, Maruyama, Chitose, Hamano, Yoshimitsu, Li, Tsung-Lin |
| المساهمون: | Ministry of Science and Technology, Taiwan, Academia Sinica |
| المصدر: | Nature Communications ; volume 14, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | Oxidized cysteine residues are highly reactive and can form functional covalent conjugates, of which the allosteric redox switch formed by the lysine-cysteine NOS bridge is an example. Here, we report a noncanonical FAD-dependent enzyme Orf1 that adds a glycine-derived N -formimidoyl group to glycinothricin to form the antibiotic BD-12. X-ray crystallography was used to investigate this complex enzymatic process, which showed Orf1 has two substrate-binding sites that sit 13.5 Å apart unlike canonical FAD-dependent oxidoreductases. One site could accommodate glycine and the other glycinothricin or glycylthricin. Moreover, an intermediate-enzyme adduct with a NOS-covalent linkage was observed in the later site, where it acts as a two-scissile-bond linkage facilitating nucleophilic addition and cofactor-free decarboxylation. The chain length of nucleophilic acceptors vies with bond cleavage sites at either N–O or O–S accounting for N -formimidoylation or N -iminoacetylation. The resultant product is no longer sensitive to aminoglycoside-modifying enzymes, a strategy that antibiotic-producing species employ to counter drug resistance in competing species. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-023-38218-w |
| الإتاحة: | https://doi.org/10.1038/s41467-023-38218-wTest https://www.nature.com/articles/s41467-023-38218-w.pdfTest https://www.nature.com/articles/s41467-023-38218-wTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.77E04BAF |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-023-38218-w |
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