Impact of Single Amino Acid Substitutions in Parkinsonism Associated Deglycase-PARK7 and Their Association with Parkinson’s Disease

Farah Anjum and Namrata Joshia and Taj Mohammad and Alaa Shafie and Fahad A. Alhumaydhi and Mohammad A. Aljasir and Moyad J. S. Shahwan and Bekhzod Abdullae and Mohd Adnan and Abdelbaset Mohamed Elasbali and Pasupuleti Visweswara Rao and Md Imtaiyaz Hassan (2022) Impact of Single Amino Acid Substitutions in Parkinsonism Associated Deglycase-PARK7 and Their Association with Parkinson’s Disease. Journal of Personalized Medicine, 12. pp. 1-16. ISSN 2075-4426

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URL: https://www.mdpi.com/2075-4426/12/2/220

Abstract

Parkinsonism-associated deglycase-PARK7/DJ-1 (PARK7) is a multifunctional protein having significant roles in inflammatory and immune disorders and cell protection against oxidative stress. Mutations in PARK7 may result in the onset and progression of a few neurodegenerative disorders such as Parkinson’s disease. This study has analyzed the non-synonymous single nucleotide polymorphisms (nsSNPs) resulting in single amino acid substitutions in PARK7 to explore its disease-causing variants and their structural dysfunctions. Initially, we retrieved the mutational dataset of PARK7 from the Ensemble database and performed detailed analyses using sequence-based and structure-based approaches. The pathogenicity of the PARK7 was then performed to distinguish the destabilizing/deleterious variants. Aggregation propensity, noncovalent interactions, packing density, and solvent accessible surface area analyses were carried out on the selected pathogenic mutations. The SODA study suggested that mutations in PARK7 result in aggregation, inducing disordered helix and altering the strand propensity. The effect of mutations alters the number of hydrogen bonds and hydrophobic interactions in PARK7, as calculated from the Arpeggio server. The study indicated that the alteration in the hydrophobic contacts and frustration of the protein could alter the stability of the missense variants of the PARK7, which might result in disease progression. This study provides a detailed understanding of the destabilizing effects of single amino acid substitutions in PARK7.

Item Type:	Article
Keyword:	Parkinson’s disease protein 7 , Protein deglycase DJ-1 , Parkinson’s disease , Single amino acid substitution , Structural dysfunctions in PARK7/DJ-1
Subjects:	R Medicine > RC Internal medicine > RC31-1245 Internal medicine > RC321-571 Neurosciences. Biological psychiatry. Neuropsychiatry > RC346-429 Neurology. Diseases of the nervous system Including speech disorders
Department:	FACULTY > Faculty of Medicine and Health Sciences
Depositing User:	SITI AZIZAH BINTI IDRIS -
Date Deposited:	21 Jul 2022 16:16
Last Modified:	21 Jul 2022 16:16
URI:	https://eprints.ums.edu.my/id/eprint/33482

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