Olivia Gampp, Luca Wenchel, Prof. Peter Güntert, Prof. Roland Riek
{"title":"同核超分辨率核磁共振波谱学","authors":"Olivia Gampp, Luca Wenchel, Prof. Peter Güntert, Prof. Roland Riek","doi":"10.1002/anie.202414324","DOIUrl":null,"url":null,"abstract":"<p>In homonuclear <sup>1</sup>H NMR (nuclear magnetic resonance) spectra such as [<sup>1</sup>H,<sup>1</sup>H]-NOESY (Nuclear Overhauser Enhancement spectroscopy), which is a historic cornerstone spectrum for biomolecular NMR structural biology, hundreds to thousands of cross peaks are present within a square of approximately 100 ppm<sup>2</sup> leading to a lot of signal overlap. Spectral resolution is thus a limiting factor for unambiguous chemical shift assignment and data interpretation for dynamics and structure elucidation. Acquiring the spectra at higher magnetic fields such as at a 1.2 GHz <sup>1</sup>H frequency helps to reduce spectral crowding, since resolution scales proportionally to the magnetic field strength. Here, we show that the linewidths of cross peaks in [<sup>1</sup>H,<sup>1</sup>H]-NOESY and [<sup>1</sup>H,<sup>1</sup>H]-TOCSY spectra can be further reduced by a factor of 2–3 in each dimension by super-resolution spectroscopy. In the indirect dimension a composite exponential-cosine weighted number of scans along the time increments are recorded and digitally smoothened by a window function, while in the direct dimension an exponential-cosine window function is applied. Furthermore, measurement time saving by reduced-acquisition super-resolution (RASR) is introduced. Application to the 20 kDa protein KRAS shows that highly resolved NMR spectra suitable for automated analysis can be acquired within less than 3 hours. The method opens an avenue towards automated chemical shift assignment, dynamics and structure determination of unlabeled small and medium size proteins within 24 hours.</p>","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"63 50","pages":""},"PeriodicalIF":16.1000,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/anie.202414324","citationCount":"0","resultStr":"{\"title\":\"Homonuclear Super-Resolution NMR Spectroscopy\",\"authors\":\"Olivia Gampp, Luca Wenchel, Prof. Peter Güntert, Prof. Roland Riek\",\"doi\":\"10.1002/anie.202414324\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>In homonuclear <sup>1</sup>H NMR (nuclear magnetic resonance) spectra such as [<sup>1</sup>H,<sup>1</sup>H]-NOESY (Nuclear Overhauser Enhancement spectroscopy), which is a historic cornerstone spectrum for biomolecular NMR structural biology, hundreds to thousands of cross peaks are present within a square of approximately 100 ppm<sup>2</sup> leading to a lot of signal overlap. Spectral resolution is thus a limiting factor for unambiguous chemical shift assignment and data interpretation for dynamics and structure elucidation. Acquiring the spectra at higher magnetic fields such as at a 1.2 GHz <sup>1</sup>H frequency helps to reduce spectral crowding, since resolution scales proportionally to the magnetic field strength. Here, we show that the linewidths of cross peaks in [<sup>1</sup>H,<sup>1</sup>H]-NOESY and [<sup>1</sup>H,<sup>1</sup>H]-TOCSY spectra can be further reduced by a factor of 2–3 in each dimension by super-resolution spectroscopy. In the indirect dimension a composite exponential-cosine weighted number of scans along the time increments are recorded and digitally smoothened by a window function, while in the direct dimension an exponential-cosine window function is applied. Furthermore, measurement time saving by reduced-acquisition super-resolution (RASR) is introduced. Application to the 20 kDa protein KRAS shows that highly resolved NMR spectra suitable for automated analysis can be acquired within less than 3 hours. The method opens an avenue towards automated chemical shift assignment, dynamics and structure determination of unlabeled small and medium size proteins within 24 hours.</p>\",\"PeriodicalId\":125,\"journal\":{\"name\":\"Angewandte Chemie International Edition\",\"volume\":\"63 50\",\"pages\":\"\"},\"PeriodicalIF\":16.1000,\"publicationDate\":\"2024-09-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/anie.202414324\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Angewandte Chemie International Edition\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/anie.202414324\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Angewandte Chemie International Edition","FirstCategoryId":"92","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/anie.202414324","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
In homonuclear 1H NMR (nuclear magnetic resonance) spectra such as [1H,1H]-NOESY (Nuclear Overhauser Enhancement spectroscopy), which is a historic cornerstone spectrum for biomolecular NMR structural biology, hundreds to thousands of cross peaks are present within a square of approximately 100 ppm2 leading to a lot of signal overlap. Spectral resolution is thus a limiting factor for unambiguous chemical shift assignment and data interpretation for dynamics and structure elucidation. Acquiring the spectra at higher magnetic fields such as at a 1.2 GHz 1H frequency helps to reduce spectral crowding, since resolution scales proportionally to the magnetic field strength. Here, we show that the linewidths of cross peaks in [1H,1H]-NOESY and [1H,1H]-TOCSY spectra can be further reduced by a factor of 2–3 in each dimension by super-resolution spectroscopy. In the indirect dimension a composite exponential-cosine weighted number of scans along the time increments are recorded and digitally smoothened by a window function, while in the direct dimension an exponential-cosine window function is applied. Furthermore, measurement time saving by reduced-acquisition super-resolution (RASR) is introduced. Application to the 20 kDa protein KRAS shows that highly resolved NMR spectra suitable for automated analysis can be acquired within less than 3 hours. The method opens an avenue towards automated chemical shift assignment, dynamics and structure determination of unlabeled small and medium size proteins within 24 hours.
期刊介绍:
Angewandte Chemie, a journal of the German Chemical Society (GDCh), maintains a leading position among scholarly journals in general chemistry with an impressive Impact Factor of 16.6 (2022 Journal Citation Reports, Clarivate, 2023). Published weekly in a reader-friendly format, it features new articles almost every day. Established in 1887, Angewandte Chemie is a prominent chemistry journal, offering a dynamic blend of Review-type articles, Highlights, Communications, and Research Articles on a weekly basis, making it unique in the field.