An NMR-Based Biosensor to Measure Stereospecific Methionine Sulfoxide Reductase Activities in Vitro and in Vivo*.


Journal

Chemistry (Weinheim an der Bergstrasse, Germany)
ISSN: 1521-3765
Titre abrégé: Chemistry
Pays: Germany
ID NLM: 9513783

Informations de publication

Date de publication:
20 Nov 2020
Historique:
received: 01 06 2020
pubmed: 6 6 2020
medline: 17 2 2021
entrez: 6 6 2020
Statut: ppublish

Résumé

Oxidation of protein methionines to methionine-sulfoxides (MetOx) is associated with several age-related diseases. In healthy cells, MetOx is reduced to methionine by two families of conserved methionine sulfoxide reductase enzymes, MSRA and MSRB that specifically target the S- or R-diastereoisomers of methionine-sulfoxides, respectively. To directly interrogate MSRA and MSRB functions in cellular settings, we developed an NMR-based biosensor that we call CarMetOx to simultaneously measure both enzyme activities in single reaction setups. We demonstrate the suitability of our strategy to delineate MSR functions in complex biological environments, including cell lysates and live zebrafish embryos. Thereby, we establish differences in substrate specificities between prokaryotic and eukaryotic MSRs and introduce CarMetOx as a highly sensitive tool for studying therapeutic targets of oxidative stress-related human diseases and redox regulated signaling pathways.

Identifiants

pubmed: 32501570
doi: 10.1002/chem.202002645
doi:

Substances chimiques

Methionine AE28F7PNPL
Methionine Sulfoxide Reductases EC 1.8.4.-

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

14838-14843

Informations de copyright

© 2020 Wiley-VCH GmbH.

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Auteurs

Carolina Sánchez-López (C)

Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET-UNR), Ocampo y Esmeralda, 2000, Rosario, Argentina.

Natalia Labadie (N)

Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET-UNR), Ocampo y Esmeralda, 2000, Rosario, Argentina.

Verónica A Lombardo (VA)

Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET-UNR), Ocampo y Esmeralda, 2000, Rosario, Argentina.
Centro de Estudios Interdisciplinarios (CEI), Universidad Nacional de Rosario, 2000, Rosario, Argentina.

Franco A Biglione (FA)

Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET-UNR), Ocampo y Esmeralda, 2000, Rosario, Argentina.

Bruno Manta (B)

Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Facultad de Medicina, Departamento de Bioquímica and Centro de Investigaciones Biomédicas, Universidad de la República, CP, 11800, Montevideo, Uruguay.

Reeba Susan Jacob (RS)

Department of Biological Regulation, Weizmann Institute of Science, 234 Herzl Street, 761000, Rehovot, Israel.

Vadim N Gladyshev (VN)

Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.

Salim Abdelilah-Seyfried (S)

Institute of Biochemistry and Biology, Potsdam University, 14476, Potsdam, Germany.
Institute of Molecular Biology, Hannover Medical School, 30625, Hannover, Germany.

Philipp Selenko (P)

Department of Biological Regulation, Weizmann Institute of Science, 234 Herzl Street, 761000, Rehovot, Israel.

Andres Binolfi (A)

Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET-UNR), Ocampo y Esmeralda, 2000, Rosario, Argentina.
Plataforma Argentina de Biología EstructuralyMetabolómica (PLABEM), Ocampo y Esmeralda, 2000, Rosario, Argentina.

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