2wul

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

spinqualitylabelsall models 2wul, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2wul is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: CL, FES, GSH, PEG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GLRX5_HUMAN Adult-onset autosomal recessive sideroblastic anemia. The disease is caused by mutations affecting the gene represented in this entry. Function GLRX5_HUMAN Monothiol glutaredoxin involved in the biogenesis of iron-sulfur clusters. Required for normal iron homeostasis. Required for normal regulation of hemoglobin synthesis by the iron-sulfur protein ACO1. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Human glutaredoxin 5 (GLRX5) is an evolutionarily conserved thiol-disulfide oxidoreductase that has a direct role in the maintenance of normal cytosolic and mitochondrial iron homeostasis and its expression affects haem biosynthesis and erythropoiesis. We have crystallised the human GLRX5 bound to two [2Fe2S] clusters and four glutathione (GSH) molecules. The crystal structure revealed a tetrameric organisation with the [2Fe2S] clusters buried in the interior and shielded from the solvent by the conserved beta1-alpha2 loop, Phe69 and the GSH molecules. Each [2Fe2S] cluster is ligated by the N-terminal active site cysteine (Cys67) thiols contributed by two protomers and two cysteine thiols from two GSH. The two subunits coordinating the cluster are in a more extended conformation compared to FeS-bound human GLRX2 and the intersubunit interactions are more extensive and involve conserved residues among monothiol GLRXs. Gelfiltration chromatography and analytical ultracentrifugation supported a tetrameric organisation of holo GLRX5 while the apo protein is monomeric. Mass spectrometry analyses revealed glutathionylation of the cysteines in the absence of the [2Fe2S] 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 slower than GLRX2 and was active as a glutathione-dependent electron donor for mammalian ribonucleotide reductase. The Crystal structure of human GLRX5: iron sulphur cluster coordination, tetrameric assembly and monomer activity.,Johansson C, Roos AK, Montano SJ, Sengupta R, Filippakopoulos P, Guo K, von Delft F, Holmgren A, Oppermann U, Kavanagh KL Biochem J. 2010 Oct 29. PMID:21029046 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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