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Mutational Landscape of Pirin and Elucidation of the Impact of Most Detrimental Missense Variants That Accelerate the Breast Cancer Pathways: A Computational Modelling Study
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 tumor formation, and metastasis, through an enforced transition of G1/S phase of the cell cycle by upregula...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273169/ https://www.ncbi.nlm.nih.gov/pubmed/34262943 http://dx.doi.org/10.3389/fmolb.2021.692835 |
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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. |
author_facet | 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. |
author_sort | Suleman, Muhammad |
collection | PubMed |
description | 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 tumor 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 humans, we used a variety of computational tools to identify non-synonymous single-nucleotide polymorphisms (SNPs) 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 by consensus, 24 mutations were confirmed to be deleterious in nature. Mutations such as V257A, I28T, and I264S were unveiled as highly destabilizing due to a 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. |
format | Online Article Text |
id | pubmed-8273169 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82731692021-07-13 Mutational Landscape of Pirin and Elucidation of the Impact of Most Detrimental Missense Variants That Accelerate the Breast Cancer Pathways: A Computational Modelling Study 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. Front Mol Biosci Molecular Biosciences 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 tumor 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 humans, we used a variety of computational tools to identify non-synonymous single-nucleotide polymorphisms (SNPs) 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 by consensus, 24 mutations were confirmed to be deleterious in nature. Mutations such as V257A, I28T, and I264S were unveiled as highly destabilizing due to a 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. Frontiers Media S.A. 2021-06-28 /pmc/articles/PMC8273169/ /pubmed/34262943 http://dx.doi.org/10.3389/fmolb.2021.692835 Text en Copyright © 2021 Suleman, Tahir ul Qamar, Saleem, Ahmad, Ali, Khan, Akbar, Khan, Alblihy, Alrumaihi, Waseem and Allemailem. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences 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. Mutational Landscape of Pirin and Elucidation of the Impact of Most Detrimental Missense Variants That Accelerate the Breast Cancer Pathways: A Computational Modelling Study |
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 |
title_full | Mutational Landscape of Pirin and Elucidation of the Impact of Most Detrimental Missense Variants That Accelerate the Breast Cancer Pathways: A Computational Modelling Study |
title_fullStr | Mutational Landscape of Pirin and Elucidation of the Impact of Most Detrimental Missense Variants That Accelerate the Breast Cancer Pathways: A Computational Modelling Study |
title_full_unstemmed | Mutational Landscape of Pirin and Elucidation of the Impact of Most Detrimental Missense Variants That Accelerate the Breast Cancer Pathways: A Computational Modelling Study |
title_short | Mutational Landscape of Pirin and Elucidation of the Impact of Most Detrimental Missense Variants That Accelerate the Breast Cancer Pathways: A Computational Modelling Study |
title_sort | mutational landscape of pirin and elucidation of the impact of most detrimental missense variants that accelerate the breast cancer pathways: a computational modelling study |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273169/ https://www.ncbi.nlm.nih.gov/pubmed/34262943 http://dx.doi.org/10.3389/fmolb.2021.692835 |
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