ALS has a worldwide annual incidence of approximately 1.5 to 2 cases/100,000 and a prevalence of 6-8 cases/100,000. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist.Īmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the adult onset of progressive dysfunction and loss of upper motor neurons in the motor cortex and lower motor neurons in the brainstem, spinal cord, and their associated tracts. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: LGAM received a fellowship from Faperj (E-26/102.372/2011), LCP and PRD received a fellowship from the Federal University of Rio de Janeiro State (UNIRIO), Rio de Janeiro, Brazil. Received: JAccepted: OctoPublished: December 2, 2013Ĭopyright: © 2013 Moreira et al. PLoS ONE 8(12):Įditor: Weidong Le, Institute of Health Science, China Ĭitation: Moreira LGA, Pereira LC, Drummond PR, De Mesquita JF (2013) Structural and Functional Analysis of Human SOD1 in Amyotrophic Lateral Sclerosis. The SOD1 database converge structural and functional analyses of SOD1 it is a vast resource for the molecular analysis of amyotrophic lateral sclerosis, which allows the user to expand his knowledge on the molecular basis of the disease. In the structural analysis, all models showed conformational changes when compared to wild-type SOD1, and the degree of structural alignment varied between them. The results of this functional analysis indicate that the majority of the 124 natural mutants are harmful to the protein structure and thus corroborate the correlation between the reported mutations and fALS. A human-curated database was developed using the server side include in Java, JMOL. Models were aligned with the native protein by the TM-align algorithm. For the structural analysis, theoretical models of 124 SNPs of SOD1 were created by comparative modeling using the MHOLline workflow, which includes Modeller and Procheck. Eleven different algorithms were used to estimate the functional impact of the replacement of one amino acid on protein structure: SNPs&GO, PolyPhen-2, SNAP, PMUT, Sift, PhD-SNP, nsSNPAnalyzer, TANGO, WALTZ, LIMBO and FoldX. We performed a functional analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in 124 fALS SOD1 mutants. More than 100 mutations in the SOD1 gene have been associated with fALS, altering the geometry of the active site, protein folding and the interaction between monomers. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with familial inheritance (fALS) in 5% to 10% of cases 25% of those are caused by mutations in the superoxide dismutase 1 (SOD1) protein.
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