NQO1 rs1800566 polymorph is more prone to NOx induced lung injury: Endorsing deleterious functionality through informatics approach

作者：Basharat Zarrin^*; Messaoudi Abdelmonaem; Ruba Sehrish; Yasmin Azra

来源：Gene, 2016, 591(1): 14-20.

DOI：10.1016/j.gene.2016.06.048

• NQO1
• NOx
• rs1800566
• Functional analysis
• Bioinformatics

Gene-environment interaction studies have led to the identification of genetic mutations in individuals with increased susceptibility to pollution related diseases. rs1800566 polymorphism of NQO1, leading to P187S missense mutation in the transcribed antioxidant protein, causes individuals carrying this mutation more prone to NO2 induced lung inflammatory injury. Here, we report significant structural and functional changes incurred by NQO1 antioxidant protein as a result of alteration in its nucleotide (C609T) and hence, protein sequence. Detailed insights were obtained regarding the prospective impact of this mutation on the structural stability of normal and mutated NQO1 protein, using a myriad of bioinformatic tools and webservers. Structure analysis showed no significant change at secondary level. A change in the native backbone conformation was observed due to formation of a hydrogen bond. Hydrophobicity and phosphorylation properties, decisive factors for functioning and stability of NQO1 were considerably influenced by P187S mutation. Computational study of the properties of a polymorph linked with NOx induced lung injury sheds light on the molecular basis of this polymorphism and endorses previous findings, reported by the scientists working in this domain.

• 出版日期2016-10-10