Computational Analysis of nsSNPs of ADA Gene in Severe Combined Immunodeficiency Using Molecular Modeling and Dynamics Simulation
Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiency (PID), characterized by fatal opportunistic infections. The ADA gene encodes adenosine deaminase, an enzyme that catalyzes the irreversible deamination of adenosine and deoxyadenosine in the catabolic pathway...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2019/5902391 |
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| author | Soukaina Essadssi Al Mehdi Krami Lamiae Elkhattabi Zouhair Elkarhat Ghita Amalou Houria Abdelghaffar Hassan Rouba Abdelhamid Barakat |
| author_facet | Soukaina Essadssi Al Mehdi Krami Lamiae Elkhattabi Zouhair Elkarhat Ghita Amalou Houria Abdelghaffar Hassan Rouba Abdelhamid Barakat |
| author_sort | Soukaina Essadssi |
| collection | DOAJ |
| description | Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiency (PID), characterized by fatal opportunistic infections. The ADA gene encodes adenosine deaminase, an enzyme that catalyzes the irreversible deamination of adenosine and deoxyadenosine in the catabolic pathway of purine. Mutations of the ADA gene have been identified in patients with severe combined immunodeficiency. In this study, we performed a bioinformatics analysis of the human ADA gene to identify potentially harmful nonsynonymous SNPs and their effect on protein structure and stability. Using eleven prediction tools, we identified 15 nsSNPs (H15D, H15P, H17Q, H17Y, D19N, T26I, G140E, C153F, A183D, G216R, H258Y, C262Y, S291L, S291W, and K34OE) as harmful. The results of ConSurf’s analysis revealed that all these nsSNPs are localised in the highly conserved positions and affect the structure of the native proteins. In addition, our computational analysis showed that the H15D, G140E, G216R, and S291L mutations identified as being associated with severe combined immunodeficiency affect protein structure. Similarly, the results of the analyses of Rmsd, Rmsf, and Rg showed that all these factors influence protein stability, flexibility, and compaction with different levels of impact. This study is the first comprehensive computational analysis of nsSNPs of the ADA gene. However, functional analyses are needed to elucidate the biological mechanisms of these polymorphisms in severe combined immunodeficiency. |
| format | Article |
| id | doaj-art-e85042a2409444ac95a68039de425c73 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-e85042a2409444ac95a68039de425c732025-02-03T06:05:23ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/59023915902391Computational Analysis of nsSNPs of ADA Gene in Severe Combined Immunodeficiency Using Molecular Modeling and Dynamics SimulationSoukaina Essadssi0Al Mehdi Krami1Lamiae Elkhattabi2Zouhair Elkarhat3Ghita Amalou4Houria Abdelghaffar5Hassan Rouba6Abdelhamid Barakat7Laboratory 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, Integrated and Molecular Functional Exploration (LBEFIM), Faculty of Science and Techniques of Mohammedia, Hassan II University of Casablanca, 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, MoroccoSevere combined immunodeficiency (SCID) is the most severe form of primary immunodeficiency (PID), characterized by fatal opportunistic infections. The ADA gene encodes adenosine deaminase, an enzyme that catalyzes the irreversible deamination of adenosine and deoxyadenosine in the catabolic pathway of purine. Mutations of the ADA gene have been identified in patients with severe combined immunodeficiency. In this study, we performed a bioinformatics analysis of the human ADA gene to identify potentially harmful nonsynonymous SNPs and their effect on protein structure and stability. Using eleven prediction tools, we identified 15 nsSNPs (H15D, H15P, H17Q, H17Y, D19N, T26I, G140E, C153F, A183D, G216R, H258Y, C262Y, S291L, S291W, and K34OE) as harmful. The results of ConSurf’s analysis revealed that all these nsSNPs are localised in the highly conserved positions and affect the structure of the native proteins. In addition, our computational analysis showed that the H15D, G140E, G216R, and S291L mutations identified as being associated with severe combined immunodeficiency affect protein structure. Similarly, the results of the analyses of Rmsd, Rmsf, and Rg showed that all these factors influence protein stability, flexibility, and compaction with different levels of impact. This study is the first comprehensive computational analysis of nsSNPs of the ADA gene. However, functional analyses are needed to elucidate the biological mechanisms of these polymorphisms in severe combined immunodeficiency.http://dx.doi.org/10.1155/2019/5902391 |
| spellingShingle | Soukaina Essadssi Al Mehdi Krami Lamiae Elkhattabi Zouhair Elkarhat Ghita Amalou Houria Abdelghaffar Hassan Rouba Abdelhamid Barakat Computational Analysis of nsSNPs of ADA Gene in Severe Combined Immunodeficiency Using Molecular Modeling and Dynamics Simulation Journal of Immunology Research |
| title | Computational Analysis of nsSNPs of ADA Gene in Severe Combined Immunodeficiency Using Molecular Modeling and Dynamics Simulation |
| title_full | Computational Analysis of nsSNPs of ADA Gene in Severe Combined Immunodeficiency Using Molecular Modeling and Dynamics Simulation |
| title_fullStr | Computational Analysis of nsSNPs of ADA Gene in Severe Combined Immunodeficiency Using Molecular Modeling and Dynamics Simulation |
| title_full_unstemmed | Computational Analysis of nsSNPs of ADA Gene in Severe Combined Immunodeficiency Using Molecular Modeling and Dynamics Simulation |
| title_short | Computational Analysis of nsSNPs of ADA Gene in Severe Combined Immunodeficiency Using Molecular Modeling and Dynamics Simulation |
| title_sort | computational analysis of nssnps of ada gene in severe combined immunodeficiency using molecular modeling and dynamics simulation |
| url | http://dx.doi.org/10.1155/2019/5902391 |
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