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Fenton-Chemistry-Based Oxidative Modification of Proteins Reflects Their Conformation

Nehls, Thomas ; Heymann, Tim ; Meyners, Christian ; Hausch, Felix ; Lermyte, Frederik (2022):
Fenton-Chemistry-Based Oxidative Modification of Proteins Reflects Their Conformation. (Publisher's Version)
In: International Journal of Molecular Sciences, 22 (18), MDPI, e-ISSN 1422-0067,
DOI: 10.26083/tuprints-00021257,

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Item Type: Article
Origin: Secondary publication via sponsored Golden Open Access
Status: Publisher's Version
Title: Fenton-Chemistry-Based Oxidative Modification of Proteins Reflects Their Conformation
Language: English

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.

Journal or Publication Title: International Journal of Molecular Sciences
Volume of the journal: 22
Issue Number: 18
Place of Publication: Darmstadt
Publisher: MDPI
Collation: 18 Seiten
Classification DDC: 500 Naturwissenschaften und Mathematik > 540 Chemie
500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
Divisions: 07 Department of Chemistry > Fachgebiet Biochemie
Date Deposited: 06 May 2022 12:06
Last Modified: 23 Aug 2022 11:52
DOI: 10.26083/tuprints-00021257
Corresponding Links:
URN: urn:nbn:de:tuda-tuprints-212576
Additional Information:

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

URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/21257
PPN: 494615834
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