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Computational Analysis of Missense Variants in the Human Transmembrane Protease Serine 2 (TMPRSS2) and SARS-CoV-2

The human transmembrane protease serine 2 (TMPRSS2) protein plays an important role in prostate cancer progression. It also facilitates viral entry into target cells by proteolytically cleaving and activating the S protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the c...

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Autores principales: Saih, Asmae, Bouqdayr, Meryem, Baba, Hanâ, Hamdi, Salsabil, Moussamih, Samya, Bennani, Houda, Saile, Rachid, Wakrim, Lahcen, Kettani, Anass
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531787/
https://www.ncbi.nlm.nih.gov/pubmed/34692848
http://dx.doi.org/10.1155/2021/9982729
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author Saih, Asmae
Bouqdayr, Meryem
Baba, Hanâ
Hamdi, Salsabil
Moussamih, Samya
Bennani, Houda
Saile, Rachid
Wakrim, Lahcen
Kettani, Anass
author_facet Saih, Asmae
Bouqdayr, Meryem
Baba, Hanâ
Hamdi, Salsabil
Moussamih, Samya
Bennani, Houda
Saile, Rachid
Wakrim, Lahcen
Kettani, Anass
author_sort Saih, Asmae
collection PubMed
description The human transmembrane protease serine 2 (TMPRSS2) protein plays an important role in prostate cancer progression. It also facilitates viral entry into target cells by proteolytically cleaving and activating the S protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the current study, we used different available tools like SIFT, PolyPhen2.0, PROVEAN, SNAP2, PMut, MutPred2, I-Mutant Suite, MUpro, iStable, ConSurf, ModPred, SwissModel, PROCHECK, Verify3D, and TM-align to identify the most deleterious variants and to explore possible effects on the TMPRSS2 stability, structure, and function. The six missense variants tested were evaluated to have deleterious effects on the protein by SIFT, PolyPhen2.0, PROVEAN, SNAP2, and PMut. Additionally, V160M, G181R, R240C, P335L, G432A, and D435Y variants showed a decrease in stability by at least 2 servers; G181R, G432A, and D435Y are highly conserved and identified posttranslational modifications sites (PTMs) for proteolytic cleavage and ADP-ribosylation using ConSurf and ModPred servers. The 3D structure of TMPRSS2 native and mutants was generated using 7 meq as a template from the SwissModeller group, refined by ModRefiner, and validated using the Ramachandran plot. Hence, this paper can be advantageous to understand the association between these missense variants rs12329760, rs781089181, rs762108701, rs1185182900, rs570454392, and rs867186402 and susceptibility to SARS-CoV-2.
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spelling pubmed-85317872021-10-23 Computational Analysis of Missense Variants in the Human Transmembrane Protease Serine 2 (TMPRSS2) and SARS-CoV-2 Saih, Asmae Bouqdayr, Meryem Baba, Hanâ Hamdi, Salsabil Moussamih, Samya Bennani, Houda Saile, Rachid Wakrim, Lahcen Kettani, Anass Biomed Res Int Research Article The human transmembrane protease serine 2 (TMPRSS2) protein plays an important role in prostate cancer progression. It also facilitates viral entry into target cells by proteolytically cleaving and activating the S protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the current study, we used different available tools like SIFT, PolyPhen2.0, PROVEAN, SNAP2, PMut, MutPred2, I-Mutant Suite, MUpro, iStable, ConSurf, ModPred, SwissModel, PROCHECK, Verify3D, and TM-align to identify the most deleterious variants and to explore possible effects on the TMPRSS2 stability, structure, and function. The six missense variants tested were evaluated to have deleterious effects on the protein by SIFT, PolyPhen2.0, PROVEAN, SNAP2, and PMut. Additionally, V160M, G181R, R240C, P335L, G432A, and D435Y variants showed a decrease in stability by at least 2 servers; G181R, G432A, and D435Y are highly conserved and identified posttranslational modifications sites (PTMs) for proteolytic cleavage and ADP-ribosylation using ConSurf and ModPred servers. The 3D structure of TMPRSS2 native and mutants was generated using 7 meq as a template from the SwissModeller group, refined by ModRefiner, and validated using the Ramachandran plot. Hence, this paper can be advantageous to understand the association between these missense variants rs12329760, rs781089181, rs762108701, rs1185182900, rs570454392, and rs867186402 and susceptibility to SARS-CoV-2. Hindawi 2021-10-19 /pmc/articles/PMC8531787/ /pubmed/34692848 http://dx.doi.org/10.1155/2021/9982729 Text en Copyright © 2021 Asmae Saih et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Saih, Asmae
Bouqdayr, Meryem
Baba, Hanâ
Hamdi, Salsabil
Moussamih, Samya
Bennani, Houda
Saile, Rachid
Wakrim, Lahcen
Kettani, Anass
Computational Analysis of Missense Variants in the Human Transmembrane Protease Serine 2 (TMPRSS2) and SARS-CoV-2
title Computational Analysis of Missense Variants in the Human Transmembrane Protease Serine 2 (TMPRSS2) and SARS-CoV-2
title_full Computational Analysis of Missense Variants in the Human Transmembrane Protease Serine 2 (TMPRSS2) and SARS-CoV-2
title_fullStr Computational Analysis of Missense Variants in the Human Transmembrane Protease Serine 2 (TMPRSS2) and SARS-CoV-2
title_full_unstemmed Computational Analysis of Missense Variants in the Human Transmembrane Protease Serine 2 (TMPRSS2) and SARS-CoV-2
title_short Computational Analysis of Missense Variants in the Human Transmembrane Protease Serine 2 (TMPRSS2) and SARS-CoV-2
title_sort computational analysis of missense variants in the human transmembrane protease serine 2 (tmprss2) and sars-cov-2
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531787/
https://www.ncbi.nlm.nih.gov/pubmed/34692848
http://dx.doi.org/10.1155/2021/9982729
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