Nehls, Thomas ; Heymann, Tim ; Meyners, Christian ; Hausch, Felix ; Lermyte, Frederik (2022)
Fenton-Chemistry-Based Oxidative Modification of Proteins Reflects Their Conformation.
In: International Journal of Molecular Sciences, 22 (18)
doi: 10.3390/ijms22189927
Artikel, Bibliographie
Dies ist die neueste Version dieses Eintrags.
Kurzbeschreibung (Abstract)
In order to understand protein structure to a sufficient extent for, e.g., drug discovery, no single technique can provide satisfactory information on both the lowest-energy conformation and on dynamic changes over time (the ‘four-dimensional’ protein structure). Instead, a combination of complementary techniques is required. Mass spectrometry methods have shown promise in addressing protein dynamics, but often rely on the use of high-end commercial or custom instruments. Here, we apply well-established chemistry to conformation-sensitive oxidative protein labelling on a timescale of a few seconds, followed by analysis through a routine protein analysis workflow. For a set of model proteins, we show that site selectivity of labelling can indeed be rationalised in terms of known structural information, and that conformational changes induced by ligand binding are reflected in the modification pattern. In addition to conventional bottom-up analysis, further insights are obtained from intact mass measurement and native mass spectrometry. We believe that this method will provide a valuable and robust addition to the ‘toolbox’ of mass spectrometry researchers studying higher-order protein structure.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2022 |
| Autor(en): | Nehls, Thomas ; Heymann, Tim ; Meyners, Christian ; Hausch, Felix ; Lermyte, Frederik |
| Art des Eintrags: | Bibliographie |
| Titel: | Fenton-Chemistry-Based Oxidative Modification of Proteins Reflects Their Conformation |
| Sprache: | Englisch |
| Publikationsjahr: | 2022 |
| Verlag: | MDPI |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | International Journal of Molecular Sciences |
| Jahrgang/Volume einer Zeitschrift: | 22 |
| (Heft-)Nummer: | 18 |
| Kollation: | 18 Seiten |
| DOI: | 10.3390/ijms22189927 |
| Zugehörige Links: | |
| Kurzbeschreibung (Abstract): | In order to understand protein structure to a sufficient extent for, e.g., drug discovery, no single technique can provide satisfactory information on both the lowest-energy conformation and on dynamic changes over time (the ‘four-dimensional’ protein structure). Instead, a combination of complementary techniques is required. Mass spectrometry methods have shown promise in addressing protein dynamics, but often rely on the use of high-end commercial or custom instruments. Here, we apply well-established chemistry to conformation-sensitive oxidative protein labelling on a timescale of a few seconds, followed by analysis through a routine protein analysis workflow. For a set of model proteins, we show that site selectivity of labelling can indeed be rationalised in terms of known structural information, and that conformational changes induced by ligand binding are reflected in the modification pattern. In addition to conventional bottom-up analysis, further insights are obtained from intact mass measurement and native mass spectrometry. We believe that this method will provide a valuable and robust addition to the ‘toolbox’ of mass spectrometry researchers studying higher-order protein structure. |
| Zusätzliche Informationen: | Data Availability Statement: The data and materials underlying this article will be shared on request to the corresponding author. Keywords: mass spectrometry; protein folding; protein–ligand interactions; protein dynamics; FK506-binding protein; FKBP12; FKBP51 |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 540 Chemie 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie |
| Fachbereich(e)/-gebiet(e): | 07 Fachbereich Chemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut |
| Hinterlegungsdatum: | 02 Aug 2024 12:40 |
| Letzte Änderung: | 02 Aug 2024 12:40 |
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| Suche nach Titel in: | TUfind oder in Google |
Verfügbare Versionen dieses Eintrags
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Fenton-Chemistry-Based Oxidative Modification of Proteins Reflects Their Conformation. (deposited 06 Mai 2022 12:06)
- Fenton-Chemistry-Based Oxidative Modification of Proteins Reflects Their Conformation. (deposited 02 Aug 2024 12:40) [Gegenwärtig angezeigt]
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