Revealing arginine-cysteine and glycine-cysteine NOS linkages by a systematic re-evaluation of protein structures
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| Publicado en: | Communications Chemistry vol. 8, no. 1 (2025), p. 146 |
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| Publicado: |
Nature Publishing Group
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| Materias: | |
| Acceso en línea: | Citation/Abstract Full Text - PDF |
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| Resumen: | Nitrogen-oxygen-sulfur (NOS) linkages act as allosteric redox switches, modulating enzymatic activity in response to redox fluctuations. While NOS linkages in proteins were once assumed to occur only between lysine and cysteine, our investigation shows that these bonds extend beyond the well–studied lysine-NOS-cysteine examples. By systematically analyzing over 86,000 high–resolution X-ray protein structures, we uncovered 69 additional NOS bonds, including arginine-NOS-cysteine and glycine-NOS-cysteine. Our pipeline integrates machine learning, quantum–mechanical calculations, and high-resolution X-ray crystallographic data to systematically detect these subtle covalent interactions and identify key predictive descriptors for their formation. The discovery of these previously unrecognized linkages broadens the scope of protein chemistry and may enable targeted modulation in drug design and protein engineering. Although our study focuses on NOS linkages, the flexibility of this methodology allows for the investigation of a wide range of chemical bonds and covalent modifications, including structurally resolvable posttranslational modifications (PTMs). By revisiting and re-examining well-established protein models, this work underscores how systematic data-driven approaches can uncover hidden aspects of protein chemistry and inspire deeper insights into protein function and stability.Nitrogen-oxygen-sulfur (NOS) linkages serve as crucial allosteric redox switches in proteins, yet their diversity beyond lysine-cysteine pairs remains underexplored. Here, the authors employ machine learning and quantum-mechanical calculations to identify 69 NOS bonds, expanding protein chemistry’s landscape and offering new avenues for drug design and protein engineering. |
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| ISSN: | 2399-3669 |
| DOI: | 10.1038/s42004-025-01535-w |
| Fuente: | Materials Science Database |