An unusual mode of iron-sulfur-cluster coordination in a teleost glutaredoxin
- Authors
- Bräutigam, L., Johansson, C., Kubsch, B., McDonough, M.A., Bill, E., Holmgren, A., and Berndt, C.
- ID
- ZDB-PUB-130709-50
- Date
- 2013
- Source
- Biochemical and Biophysical Research Communications 436(3): 491-496 (Journal)
- Registered Authors
- Keywords
- Grx, glutaredoxin, GSH, glutathion, GSSG, glutathione disulphide, HED, hydroxyethyl disulphide, Trx, thioredoxin
- MeSH Terms
-
- Amino Acid Motifs
- Animals
- Catalytic Domain
- Cysteine/chemistry
- Enzyme Activation
- Glutaredoxins/chemistry*
- Humans
- Iron-Sulfur Proteins/chemistry*
- Ligands
- Molecular Sequence Data
- Protein Binding
- Protein Multimerization
- Sequence Homology, Amino Acid
- Zebrafish/metabolism*
- Zebrafish Proteins/chemistry*
- PubMed
- 23756812 Full text @ Biochem. Biophys. Res. Commun.
Glutaredoxins that contain a Cys-X-X-Cys active site motif are glutathione-dependent thiol-disulfide oxidoreductases. Vertebrate glutaredoxin 2 is characterized by two extra cysteines that form an intra-molecular disulfide bridge. Zebrafish glutaredoxin 2 contains four additional cysteines that are conserved within the infraclass of bony fish (teleosts). Here, we present a biochemical and biophysical characterization of zebrafish glutaredoxin 2, focusing on iron–sulfur-cluster coordination. The coordination of [2Fe2S]2+-clusters in monomers of this protein was revealed by both absorption and Mössbauer spectroscopy as well as size exclusion chromatography. All other holo-glutaredoxins represent [FeS]-cluster bridged dimers using two molecules of non-covalently bound glutathione and the N-terminal active site cysteines as ligands. These cysteine residues were not required for [FeS]-cluster coordination in zebrafish glutaredoxin 2. A crystal structure of the teleost protein revealed high structural similarity to its human homologue. The two vertebrate-specific cysteines as well as two of the teleost-specific cysteines are positioned within a radius of 7 Å near the C-terminus suggesting a potential role in [FeS]-cluster coordination. Indeed, mutated proteins lacking these teleost-specific cysteines lost the ability to bind the cofactor. Hence, the apparent mode of [FeS]-cluster coordination in zebrafish glutaredoxin 2 could be different from all yet described [FeS]-glutaredoxins.