| Structural highlights
Disease
[SODC_HUMAN] Defects in SOD1 are the cause of amyotrophic lateral sclerosis type 1 (ALS1) [MIM:105400]. ALS1 is a familial form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of cases leading to familial forms.[1] [2] [3] [4] [5] [6] [7] [8] [:][9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45]
Function
[SODC_HUMAN] Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
Publication Abstract from PubMed
The functional and structural significance of the intrasubunit disulfide bond in copper-zinc superoxide dismutase (SOD1) was studied by characterizing mutant forms of human and yeast SOD1 (hSOD and ySOD) lacking the disulfide bond. We determined X-ray crystal structures of metal-bound and metal-deficient hC57S SOD1. C57S hSOD1 isolated from yeast contained four zinc ions per protein dimer and was structurally very similar to wild type. Addition of copper to this four-zinc protein gave properly reconstituted 2Cu2Zn C57S hSOD, and its spectroscopic properties indicated that the coordination geometry of the copper was remarkably similar to that of holo wild-type hSOD1. In contrast, addition of copper and zinc ions to apo C57S human SOD1 failed to give proper reconstitution. Using pulse radiolysis, we determined SOD activities of yeast and human SOD1s lacking disulfide bonds and found they were enzymatically active at approximately 10% of the wild-type rate. These results are contrary to earlier reports that the intrasubunit disulfide bonds in SOD1 are essential for SOD activity. Kinetic studies revealed further that the yeast mutant SOD1 had less ionic attraction for superoxide, possibly explaining the lower rates. S. cerevisiae cells lacking the sod1 gene do not grow aerobically in the absence of lysine, but expression of C57S SOD1 increased growth to 30-50% of the growth of cells expressing wild type SOD1, supporting that C57S SOD1 retained a significant amount of activity.
Insights into the Role of the Unusual Disulfide Bond in Copper-Zinc Superoxide Dismutase.,Sea K, Sohn SH, Durazo A, Sheng Y, Shaw BF, Cao X, Taylor AB, Whitson LJ, Holloway SP, Hart PJ, Cabelli DE, Gralla EB, Valentine JS J Biol Chem. 2014 Nov 28. pii: jbc.M114.588798. PMID:25433341[46]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
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- ↑ Sea K, Sohn SH, Durazo A, Sheng Y, Shaw BF, Cao X, Taylor AB, Whitson LJ, Holloway SP, Hart PJ, Cabelli DE, Gralla EB, Valentine JS. Insights into the Role of the Unusual Disulfide Bond in Copper-Zinc Superoxide Dismutase. J Biol Chem. 2014 Nov 28. pii: jbc.M114.588798. PMID:25433341 doi:https://dx.doi.org/10.1074/jbc.M114.588798
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