These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: A theoretical study on Zn binding loop mutants instigating destabilization and metal binding loss in human SOD1 protein.
    Author: Srinivasan E, Sethumadhavan R, Rajasekaran R.
    Journal: J Mol Model; 2017 Apr; 23(4):103. PubMed ID: 28271284.
    Abstract:
    Mutations in Cu/Zn superoxide dismutase 1 (SOD1) protein are a major cause of the devastating neurodegenerative disorder Amyotrophic lateral sclerosis. Evidence suggests that SOD1 functions as a free radical scavenger in humans. However, neither the mechanism nor a cure for this neurodegenerative disease are yet known. In the present study, we explored the effect of mutations on the mechanistic action on the Zn binding loop of SOD1 through discrete molecular dynamics. The results were analyzed in detail using statistical potential (BACH) to find the mutant structures having the least potential energy. Subsequently, we studied the impact of those mutations on metal ions bound in SOD1 using the program Check My Metal. Remarkably, our results recognized certain mutants, viz. His80Arg and Asp83Gly, that were more damaging to the Zn binding loop than all other mutants, leading to a loss of Zn binding with altered coordination of the Zn ion. Furthermore, the conformational stability, compactness, and secondary structural alteration of the His80Arg and Asp83Gly mutants were monitored using distinct parameters. Hence, at low computational expense, our study provides helpful insight into this emergent neurodegenerative disorder affecting mankind.
    [Abstract] [Full Text] [Related] [New Search]