2WUL

CRYSTAL STRUCTURE OF THE HUMAN GLUTAREDOXIN 5 WITH BOUND GLUTATHIONE IN AN FES CLUSTER

Replaces:  2WEM

Summary for 2WUL

• Entry DOI: 10.2210/pdb2wul/pdb
• Descriptor: GLUTAREDOXIN RELATED PROTEIN 5, GLUTATHIONE, FE2/S2 (INORGANIC) CLUSTER, ... (6 entities in total)
• Functional Keywords: chromosome 14 open reading frame 87, oxidoreductase, thioredoxin family, glrx5, pr01238, flb4739
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Mitochondrion matrix : Q86SX6
• Total number of polymer chains: 4
• Total formula weight: 53291.12

Authors

Roos, A.K.,Johansson, C.,Guo, K.,Yue, W.W.,Pike, A.C.W.,Cooper, C.D.O.,Pilka, E.S.,Kavanagh, K.L.,Chaikuad, A.,von Delft, F.,Arrowsmith, C.H.,Weigelt, J.,Edwards, A.,Bountra, C.,Oppermann, U. (deposition date: 2009-10-06, release date: 2009-10-20, Last modification date: 2023-12-20)

Primary citation

Johansson, C.,Roos, A.K.,Montano, S.J.,Sengupta, R.,Filippakopoulos, P.,Guo, K.,von Delft, F.,Holmgren, A.,Oppermann, U.,Kavanagh, K.L.
The Crystal Structure of Human Glrx5: Iron Sulphur Cluster Coordination, Tetrameric Assembly and Monomer Activity.
Biochem.J., 433:303-, 2011

PubMed Abstract: Human GLRX5 (glutaredoxin 5) is an evolutionarily conserved thiol-disulfide oxidoreductase that has a direct role in the maintenance of normal cytosolic and mitochondrial iron homoeostasis, and its expression affects haem biosynthesis and erythropoiesis. We have crystallized the human GLRX5 bound to two [2Fe-2S] clusters and four GSH molecules. The crystal structure revealed a tetrameric organization with the [2Fe-2S] clusters buried in the interior and shielded from the solvent by the conserved β1-α2 loop, Phe⁶⁹ and the GSH molecules. Each [2Fe-2S] cluster is ligated by the N-terminal activesite cysteine (Cys⁶⁷) thiols contributed by two protomers and two cysteine thiols from two GSH. The two subunits co-ordinating the cluster are in a more extended conformation compared with iron-sulfur-bound human GLRX2, and the intersubunit interactions are more extensive and involve conserved residues among monothiol GLRXs. Gel-filtration chromatography and analytical ultracentrifugation support a tetrameric organization of holo-GLRX5, whereas the apoprotein is monomeric. MS analyses revealed glutathionylation of the cysteine residues in the absence of the [2Fe-2S] cluster, which would protect them from further oxidation and possibly facilitate cluster transfer/acceptance. Apo-GLRX5 reduced glutathione mixed disulfides with a rate 100 times lower than did GLRX2 and was active as a glutathione-dependent electron donor for mammalian ribonucleotide reductase.

PubMed: 21029046
DOI: 10.1042/BJ20101286

Experimental method

X-RAY DIFFRACTION (2.4 Å)