Prediction of the Impact of Deleterious Nonsynonymous Single Nucleotide Polymorphisms on the Human RRM2B Gene: A Molecular Modeling Study

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....

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Main Authors: Chaimaa Ait El Cadi, Al Mehdi Krami, Hicham Charoute, Zouhair Elkarhat, Najat Sifeddine, Hamid Lakhiari, Hassan Rouba, Abdelhamid Barakat, Halima Nahili
Format: Article
Language:English
Published: Hindawi Limited 2020-01-01
Series:BioMed Research International
Online Access:http://dx.doi.org/10.1155/2020/7614634
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spelling doaj-d28bb20b47e74cb1bcfcc726b4828ce22020-11-25T03:27:47ZengHindawi LimitedBioMed Research International2314-61332314-61412020-01-01202010.1155/2020/76146347614634Prediction of the Impact of Deleterious Nonsynonymous Single Nucleotide Polymorphisms on the Human RRM2B Gene: A Molecular Modeling StudyChaimaa Ait El Cadi0Al Mehdi Krami1Hicham Charoute2Zouhair Elkarhat3Najat Sifeddine4Hamid Lakhiari5Hassan Rouba6Abdelhamid Barakat7Halima Nahili8Laboratory of Genomics and Human Genetics, Institut Pasteur du Maroc, 20360 Casablanca, MoroccoLaboratory of Genomics and Human Genetics, Institut Pasteur du Maroc, 20360 Casablanca, MoroccoLaboratory of Genomics and Human Genetics, Institut Pasteur du Maroc, 20360 Casablanca, MoroccoLaboratory of Genomics and Human Genetics, Institut Pasteur du Maroc, 20360 Casablanca, MoroccoLaboratory of Genomics and Human Genetics, Institut Pasteur du Maroc, 20360 Casablanca, MoroccoLaboratory of Biosciences, Functional Integrated and Molecular Exploration-LBEFIM-, Biology Department, Faculty of Sciences and Technics of Mohammedia, University of Hassan II, Mohammedia 28806, MoroccoLaboratory of Genomics and Human Genetics, Institut Pasteur du Maroc, 20360 Casablanca, MoroccoLaboratory of Genomics and Human Genetics, Institut Pasteur du Maroc, 20360 Casablanca, MoroccoLaboratory of Genomics and Human Genetics, Institut Pasteur du Maroc, 20360 Casablanca, MoroccoRRM2B 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.http://dx.doi.org/10.1155/2020/7614634
collection DOAJ
language English
format Article
sources DOAJ
author Chaimaa Ait El Cadi
Al Mehdi Krami
Hicham Charoute
Zouhair Elkarhat
Najat Sifeddine
Hamid Lakhiari
Hassan Rouba
Abdelhamid Barakat
Halima Nahili
spellingShingle Chaimaa Ait El Cadi
Al Mehdi Krami
Hicham Charoute
Zouhair Elkarhat
Najat Sifeddine
Hamid Lakhiari
Hassan Rouba
Abdelhamid Barakat
Halima Nahili
Prediction of the Impact of Deleterious Nonsynonymous Single Nucleotide Polymorphisms on the Human RRM2B Gene: A Molecular Modeling Study
BioMed Research International
author_facet Chaimaa Ait El Cadi
Al Mehdi Krami
Hicham Charoute
Zouhair Elkarhat
Najat Sifeddine
Hamid Lakhiari
Hassan Rouba
Abdelhamid Barakat
Halima Nahili
author_sort Chaimaa Ait El Cadi
title 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_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_sort prediction of the impact of deleterious nonsynonymous single nucleotide polymorphisms on the human rrm2b gene: a molecular modeling study
publisher Hindawi Limited
series BioMed Research International
issn 2314-6133
2314-6141
publishDate 2020-01-01
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.
url http://dx.doi.org/10.1155/2020/7614634
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