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Molecular basis for the enzymatic inactivity of class III glutaredoxins on standard glutathionylated substrates

ABSTRACT: Glutaredoxins (GRXs) are small proteins that interact with the atypical tripeptide glutathione (GSH), a redox active metabolite that forms a disulfide (GSSG) upon oxidation. GRXs encoding variants of a CPYC motif at a conserved active site act as GSH-dependent thiol-disulfide oxidoreductases (class I). GRXs with a CGFS site (class II) bind GSH in a way that is non-permissive for thiol-disulfide oxidoreductase reactions and favours transient iron-sulfur cluster binding. The biochemical functions of CCxC/S-type (class III) GRXs, which are found only in land plants, have remained largely unexplored. In this study, we characterized the in vitro properties of one of the Arabidopsis thaliana class III GRXs, namely ROXY9.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Arabidopsis Thaliana (mouse-ear Cress)

SUBMITTER: Gereon Poschmann

LAB HEAD: Gereon Poschmann

PROVIDER: PXD042724 | Pride | 2025-01-14

REPOSITORIES: pride

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Molecular basis for the enzymatic inactivity of class III glutaredoxin ROXY9 on standard glutathionylated substrates.

Mrozek Pascal P Grunewald Stephan S Treffon Katrin K Poschmann Gereon G Rabe von Pappenheim Fabian F Tittmann Kai K Gatz Christiane C

Nature communications 20250111 1

Class I glutaredoxins (GRXs) are nearly ubiquitous proteins that catalyse the glutathione (GSH)-dependent reduction of mainly glutathionylated substrates. In land plants, a third class of GRXs has evolved (class III). Class III GRXs regulate the activity of TGA transcription factors through yet unexplored mechanisms. Here we show that Arabidopsis thaliana class III GRX ROXY9 is inactive as an oxidoreductase on widely used model substrates. Glutathionylation of the active site cysteine, a prerequ ...[more]

PMID: 39799154

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