AUTHOR=Suleman Muhammad , Tahir ul Qamar Muhammad , Saleem Shoaib , Ahmad Sajjad , Ali Syed Shujait , Khan Haji , Akbar Fazal , Khan Wajid , Alblihy Adel , Alrumaihi Faris , Waseem Muhammad , Allemailem Khaled S. 

TITLE=Mutational Landscape of Pirin and Elucidation of the Impact of Most Detrimental Missense Variants That Accelerate the Breast Cancer Pathways: A Computational Modelling Study

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.692835

DOI=10.3389/fmolb.2021.692835

ISSN=2296-889X

ABSTRACT=Pirin (PIR) protein is highly conserved in both prokaryotic and eukaryotic organisms. Recently it has been identified that PIR positively regulates breast cancer cell proliferation, xenograft tumour formation and metastasis, through an enforced transition of G1/S phase of the cell cycle by upregulation of E2F1 expression at the transcriptional level. Keeping in view the importance of PIR in many crucial cellular processes in human, we used a variety of computational tools to identify nsSNPs in the PIR gene that are highly deleterious for the structure and function of PIR protein. Out of 173 SNPs identified in the protein, 119 are non-synonymous and on consensus 24 mutations were confirmed as deleterious in nature. Mutations like V257A, I28T and I264S were unveiled as highly destabilizing due to significant stability fold change on the protein structure. This observation was further established through molecular dynamics (MD) simulation that demonstrated the role of the mutation in protein structure destability and affecting its internal dynamics. The findings of this study are believed to open doors to investigate the biological relevance of the mutations and drugability potential of the protein.