3gqf is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
[SODC_HUMAN] Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
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
Over 100 mutations in the gene encoding human copper-zinc superoxide dismutase (SOD1) cause an inherited form of the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS). Two pathogenic SOD1 mutations, His46Arg (H46R) and His48Gln (H48Q), affect residues that act as copper ligands in the wild type enzyme. Transgenic mice expressing a human SOD1 variant containing both mutations develop paralytic disease akin to ALS. Here we show that H46R/H48Q SOD1 possesses multiple characteristics that distinguish it from the wild type. These properties include the following: (1) an ablated copper-binding site, (2) a substantially weakened affinity for zinc, (3) a binding site for a calcium ion, (4) the ability to form stable heterocomplexes with the copper chaperone for SOD1 (CCS), and (5) compromised CCS-mediated oxidation of the intrasubunit disulfide bond in vivo. The results presented here, together with data on pathogenic SOD1 proteins coming from cell culture and transgenic mice, suggest that incomplete posttranslational modification of nascent SOD1 polypeptides via CCS may be a characteristic shared by familial ALS SOD1 mutants, leading to a population of destabilized, off-pathway folding intermediates that are toxic to motor neurons.
Structural and biophysical properties of the pathogenic SOD1 variant H46R/H48Q.,Winkler DD, Schuermann JP, Cao X, Holloway SP, Borchelt DR, Carroll MC, Proescher JB, Culotta VC, Hart PJ Biochemistry. 2009 Apr 21;48(15):3436-47. PMID:19227972[46]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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↑Winkler DD, Schuermann JP, Cao X, Holloway SP, Borchelt DR, Carroll MC, Proescher JB, Culotta VC, Hart PJ. Structural and biophysical properties of the pathogenic SOD1 variant H46R/H48Q. Biochemistry. 2009 Apr 21;48(15):3436-47. PMID:19227972 doi:10.1021/bi8021735
