Article citationsMore >>

Blaine R. Roberts PAK, John A., Tainer Elizabeth, D. Getzoff, Dean A., Malencik Sonia, R. Anderson, Valerie C., Bomben Kathrin, R. Meyer, Beckman JS. Structural Characterization of Zinc-deficient Human Superoxide Dismutase and Implications for ALS. J. Mol. Biol. 2007;373:877-890.

has been cited by the following article:


Computational Analysis of the Single nucleotide Polymorphisms that Affect Superoxide Dismutase Reveals Important Domain Related to Protein Function

1Daoud Research Group, University of Khartoum, Khartoum, Sudan

2Professor of Medicine, Senior Consultant Neurologist, University of Khartoum, Sudan

3Department of Bioinformatics, Africa City of Technology, Sudan University of Medical Science and Technology, Sudan;Division of Molecular Genetics, Institute of Human Genetics, University of Tubingen, Germany

American Journal of Biomedical Research. 2015, Vol. 3 No. 4, 58-65
DOI: 10.12691/ajbr-3-4-1
Copyright © 2015 Science and Education Publishing

Cite this paper:
Mohamed Dafaalla, Tarig Mabrouk, Omer Ali, Ibrahim Elkhidir, Mohamed Adel Taha, Mohamed A. Abdelrahim, Osman Arbab, Musaab M. alfaki, Abbashar M. Hussein, Mohamed A. Hassan. Computational Analysis of the Single nucleotide Polymorphisms that Affect Superoxide Dismutase Reveals Important Domain Related to Protein Function. American Journal of Biomedical Research. 2015; 3(4):58-65. doi: 10.12691/ajbr-3-4-1.

Correspondence to: Mohamed  Dafaalla, Daoud Research Group, University of Khartoum, Khartoum, Sudan. Email:


BACKGROUND: A major focus of neurodegeneration research involves the characterization of how the enzyme Cu, Zn superoxide dismutase is involved in amyotrophic lateral sclerosis (ALS). Despite a wealth of structural and biochemical knowledge, the mechanism by which SOD mutations promote ALS remains controversial.METHODS: GENEMANIA software was used to highlight genetic interactions of SOD1. SOD1 was investigated in dbSNP/NCBI database in May 2015. SOD1 had of 2123 SNPs; 622 were identified in human, of which 29 were in the coding region, 8 were non-synonymous SNPs (nsSNPs), 22 were in the 3'un-translated region, and 75 SNPs at 5'un-translated region. Only nsSNPs and 3'UTR SNPs were selected for analysis. Predictions of deleterious nsSNPs was performed by SIFT and Polyphen softwares. The functional impact of the deleterious SNPS was analyzed by project hope. Chimera and project hope softwares were used to highlight the changes occurred as a result of the deleterious SNPs at level of protein 3D structure. The SNPS at 3UTR region were analyzed by Polymirt software. RESULTS: Genamania revealed possible role for SoD1 in epidermal cell growth through interaction with NME2 (MIM 156491) and NCOA3 (MIM 601937) genes. Two SNPs were found to be deleterious in both SIFT and Polyphen, whereas one SNP was found deleterious in SIFT and not Polyphen. The SNPs predicted to be deleterious in both SIFT and Polyphen are rs11556621 and rs11556620. They cause change from the amino acid in position 29 from proline to glutamine, and in amino acid number 87 from asparagine to serine respectively. Both SNPs affect an amino acid at the interpro domain named "Superoxide dismutase, copper/zinc binding domain" (IPR001424) whose function is metal ion binding. The SNP rs1804450 effect was found to be a controversial that involves a change in amino acid in position 40 from threonine to isoleucine. Although this residue is part of the "Superoxide dismutase, copper/zinc binding domain" (IPR001424), its site is not conserved. Eight SNPs predicted to induce disruption or creation of mirRNA binding site. CONCLUSION: SNPs that affect metal binding domain of superoxide dismutase are the main SNPs that significantly affect enzyme structure and function.