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Prediction of the Impact of Deleterious Nonsynonymous Single Nucleotide Polymorphisms on the Human RRM2B Gene: A Molecular Modeling Study
RRM2B gene encodes ribonucleoside-diphosphate reductase subunit M2 B, the p53-inducible small subunit (p53R2) of ribonucleotide reductase (RNR), an enzyme catalyzing dNTP synthesis for mitochondrial DNA. Defects in this gene may cause severe mitochondrial disease affecting mainly the nervous system....
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399733/ https://www.ncbi.nlm.nih.gov/pubmed/32775440 http://dx.doi.org/10.1155/2020/7614634 |
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author | Ait El Cadi, Chaimaa Krami, Al Mehdi Charoute, Hicham Elkarhat, Zouhair Sifeddine, Najat Lakhiari, Hamid Rouba, Hassan Barakat, Abdelhamid Nahili, Halima |
author_facet | Ait El Cadi, Chaimaa Krami, Al Mehdi Charoute, Hicham Elkarhat, Zouhair Sifeddine, Najat Lakhiari, Hamid Rouba, Hassan Barakat, Abdelhamid Nahili, Halima |
author_sort | Ait El Cadi, Chaimaa |
collection | PubMed |
description | RRM2B gene encodes ribonucleoside-diphosphate reductase subunit M2 B, the p53-inducible small subunit (p53R2) of ribonucleotide reductase (RNR), an enzyme catalyzing dNTP synthesis for mitochondrial DNA. Defects in this gene may cause severe mitochondrial disease affecting mainly the nervous system. This study is aimed at examining the effect of deleterious nonsynonymous SNP (nsSNP) on the structure of the RRM2B protein, using a variety of prediction tools followed by a molecular modeling analysis. After using 13 algorithms, 19 nsSNPs were predicted deleterious. Among these variants, 18 decreased the protein stability and 16 were localized in very highly conserved regions. Protein 3D structure analysis showed that 18 variants changed amino acid interactions. These results concur with what has been found in experimental trials; 7 deleterious nsSNPs were previously reported in patients suffering from genetic disorders affecting the nervous system. Thus, our study will provide useful information to design more efficient and fast genetic tests to find RRM2B gene mutations. |
format | Online Article Text |
id | pubmed-7399733 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-73997332020-08-07 Prediction of the Impact of Deleterious Nonsynonymous Single Nucleotide Polymorphisms on the Human RRM2B Gene: A Molecular Modeling Study Ait El Cadi, Chaimaa Krami, Al Mehdi Charoute, Hicham Elkarhat, Zouhair Sifeddine, Najat Lakhiari, Hamid Rouba, Hassan Barakat, Abdelhamid Nahili, Halima Biomed Res Int Research Article RRM2B gene encodes ribonucleoside-diphosphate reductase subunit M2 B, the p53-inducible small subunit (p53R2) of ribonucleotide reductase (RNR), an enzyme catalyzing dNTP synthesis for mitochondrial DNA. Defects in this gene may cause severe mitochondrial disease affecting mainly the nervous system. This study is aimed at examining the effect of deleterious nonsynonymous SNP (nsSNP) on the structure of the RRM2B protein, using a variety of prediction tools followed by a molecular modeling analysis. After using 13 algorithms, 19 nsSNPs were predicted deleterious. Among these variants, 18 decreased the protein stability and 16 were localized in very highly conserved regions. Protein 3D structure analysis showed that 18 variants changed amino acid interactions. These results concur with what has been found in experimental trials; 7 deleterious nsSNPs were previously reported in patients suffering from genetic disorders affecting the nervous system. Thus, our study will provide useful information to design more efficient and fast genetic tests to find RRM2B gene mutations. Hindawi 2020-07-25 /pmc/articles/PMC7399733/ /pubmed/32775440 http://dx.doi.org/10.1155/2020/7614634 Text en Copyright © 2020 Chaimaa Ait El Cadi et al. http://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 Ait El Cadi, Chaimaa Krami, Al Mehdi Charoute, Hicham Elkarhat, Zouhair Sifeddine, Najat Lakhiari, Hamid Rouba, Hassan Barakat, Abdelhamid Nahili, Halima Prediction of the Impact of Deleterious Nonsynonymous Single Nucleotide Polymorphisms on the Human RRM2B Gene: A Molecular Modeling Study |
title | Prediction of the Impact of Deleterious Nonsynonymous Single Nucleotide Polymorphisms on the Human RRM2B Gene: A Molecular Modeling Study |
title_full | Prediction of the Impact of Deleterious Nonsynonymous Single Nucleotide Polymorphisms on the Human RRM2B Gene: A Molecular Modeling Study |
title_fullStr | Prediction of the Impact of Deleterious Nonsynonymous Single Nucleotide Polymorphisms on the Human RRM2B Gene: A Molecular Modeling Study |
title_full_unstemmed | Prediction of the Impact of Deleterious Nonsynonymous Single Nucleotide Polymorphisms on the Human RRM2B Gene: A Molecular Modeling Study |
title_short | Prediction of the Impact of Deleterious Nonsynonymous Single Nucleotide Polymorphisms on the Human RRM2B Gene: A Molecular Modeling Study |
title_sort | prediction of the impact of deleterious nonsynonymous single nucleotide polymorphisms on the human rrm2b gene: a molecular modeling study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399733/ https://www.ncbi.nlm.nih.gov/pubmed/32775440 http://dx.doi.org/10.1155/2020/7614634 |
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