Comprehensive bioinformatics analysis of structural and functional consequences of deleterious missense mutations in the human QDPR gene

Abstract

Quinonoid dihydropteridine reductase (QDPR) is an enzyme that regulates tetrahydrobiopterin (BH4), a cofactor for enzymes involved in neurotransmitter synthesis and blood pressure regulation. Reduced QDPR activity can cause dihydrobiopterin (BH2) accumulation and BH4 depletion, leading to impaired neurotransmitter synthesis, oxidative stress, and increased risk of Parkinson’s disease. A total of 10,236 SNPs were identified in the QDPR gene, with 217 being missense SNPs. Over 18 different sequence-based and structure-based tools were employed to assess the protein’s biological activity, with several computational tools identifying deleterious SNPs. Additionally, the article provides detailed information about the QDPR gene and protein structure and conservation analysis. The results showed that 10 mutations were harmful and linked to brain and central nervous system disorders, and were predicted to be oncogenic by Dr. Cancer and CScape. Following conservation analysis, the HOPE server was used to analyse the effect of six selected mutations (L14P, V15G, G23S, V54G, M107K, G151S) on the protein structure. Overall, the study provides insights into the biological and functional impact of nsSNPs on QDPR activity and the potential induced pathogenicity and oncogenicity. In the future, research can be conducted to systematically evaluate QDPR gene variation through clinical studies, investigate mutation prevalence across different geographical regions, and validate computational results with conclusive experiments.

Communicated by Ramaswamy H. Sarma

Keywords:

• Quinonoid dihydropteridine reductase
• deleterious missense mutations
• structural analysis
• functional analysis
• molecular dynamic simulations

Acknowledgements

The authors would like to express their sincere gratitude to the esteemed Management of M S Ramaiah Institute of Technology for generously providing the essential computational infrastructure imperative for conducting the research investigations. This study did not obtain any exclusive grants from commercial, public, or non-profit entities.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.