Anjum Farah, Joshia Namrata, Mohammad Taj, Shafie Alaa, Alhumaydhi Fahad A, Aljasir Mohammad A, Shahwan Moyad J S, Abdullaev Bekhzod, Adnan Mohd, Elasbali Abdelbaset Mohamed, Pasupuleti Visweswara Rao, Hassan Md Imtaiyaz
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
Department of Computer Science, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
J Pers Med. 2022 Feb 5;12(2):220. doi: 10.3390/jpm12020220.
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 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 to explore its disease-causing variants and their structural dysfunctions. Initially, we retrieved the mutational dataset of from the Ensembl database and performed detailed analyses using sequence-based and structure-based approaches. The pathogenicity of the 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 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.
帕金森病相关去糖基化酶-PARK7/DJ-1（PARK7）是一种多功能蛋白质，在炎症和免疫紊乱以及细胞抗氧化应激保护中发挥重要作用。PARK7中的突变可能导致一些神经退行性疾病如帕金森病的发生和进展。本研究分析了导致PARK7中单个氨基酸替换的非同义单核苷酸多态性（nsSNPs），以探索其致病变体及其结构功能障碍。最初，我们从Ensembl数据库中检索了PARK7的突变数据集，并使用基于序列和基于结构的方法进行了详细分析。然后对PARK7的致病性进行分析，以区分不稳定/有害变体。对选定的致病突变进行了聚集倾向、非共价相互作用、堆积密度和溶剂可及表面积分析。SODA研究表明，PARK7中的突变会导致聚集，诱导无序螺旋并改变链倾向。根据Arpeggio服务器计算，突变的影响改变了PARK7中的氢键数量和疏水相互作用。该研究表明，疏水接触的改变和蛋白质的失序可能会改变PARK7错义变体的稳定性，这可能导致疾病进展。本研究详细了解了PARK7中单个氨基酸替换的去稳定作用。
