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Functional and Structural Impact of Deleterious Missense Single Nucleotide Polymorphisms in the NR3C1, CYP3A5, and TNF-α Genes: An In Silico Analysis
Human diseases are generally influenced by SNPs (single nucleotide polymorphisms). The mutations in amino acid residues generated by deleterious SNPs contribute to the structural and functional diversity of the encoded protein. Tumor necrosis factor-α (TNF-α), Glucocorticoid receptor gene (NR3C1), a...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496109/ https://www.ncbi.nlm.nih.gov/pubmed/36139147 http://dx.doi.org/10.3390/biom12091307 |
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author | Ramayanam, Navakanth Raju Manickam, Ranjani Mahalingam, Vijayakumar Thangavel Goh, Khang Wen Ardianto, Chrismawan Ganesan, Poovi Ming, Long Chiau Ganesan, Rajanandh Muhasaparur |
author_facet | Ramayanam, Navakanth Raju Manickam, Ranjani Mahalingam, Vijayakumar Thangavel Goh, Khang Wen Ardianto, Chrismawan Ganesan, Poovi Ming, Long Chiau Ganesan, Rajanandh Muhasaparur |
author_sort | Ramayanam, Navakanth Raju |
collection | PubMed |
description | Human diseases are generally influenced by SNPs (single nucleotide polymorphisms). The mutations in amino acid residues generated by deleterious SNPs contribute to the structural and functional diversity of the encoded protein. Tumor necrosis factor-α (TNF-α), Glucocorticoid receptor gene (NR3C1), and Cytochrome P450 3A5 (CYP3A5) play a key role in glucocorticoid resistance susceptibility in humans. Possible causative mutations could be used as therapeutic targets and diagnostic markers for glucocorticoid resistance. This study evaluated the missense SNPs of TNF-α, NR3C1, and CYP3A5 to predict their impact on amino acid changes, protein interaction, and functional stability. The protein sequence of dbSNP was obtained and used online in silico method to screen deleterious mutants for the in silico analysis. In the coding regions of TNF-α, NR3C1, and CYP3A5, 14 deleterious mutations were discovered. The protein functional and stability changes in the amino acid between native and mutant energy were identified by analyzing the changes in the hydrogen bonding of these mutants from native, which were all measured using Swiss PDB and PyMOL. F446S and R439K had the highest root-mean-square deviation (RMSD) values among the 14 deleterious mutants. Additionally, the conserved region of amino acid protein interaction was analyzed. This study could aid in the discovery of new detrimental mutations in TNF-α, NR3C1, and CYP3A5, as well as the development of long-term therapy for corticosteroid resistance in several inflammatory diseases. However, more research into the deleterious mutations of the TNF-α, NR3C1, and CYP3A5 genes is needed to determine their role in corticosteroid resistance. |
format | Online Article Text |
id | pubmed-9496109 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94961092022-09-23 Functional and Structural Impact of Deleterious Missense Single Nucleotide Polymorphisms in the NR3C1, CYP3A5, and TNF-α Genes: An In Silico Analysis Ramayanam, Navakanth Raju Manickam, Ranjani Mahalingam, Vijayakumar Thangavel Goh, Khang Wen Ardianto, Chrismawan Ganesan, Poovi Ming, Long Chiau Ganesan, Rajanandh Muhasaparur Biomolecules Article Human diseases are generally influenced by SNPs (single nucleotide polymorphisms). The mutations in amino acid residues generated by deleterious SNPs contribute to the structural and functional diversity of the encoded protein. Tumor necrosis factor-α (TNF-α), Glucocorticoid receptor gene (NR3C1), and Cytochrome P450 3A5 (CYP3A5) play a key role in glucocorticoid resistance susceptibility in humans. Possible causative mutations could be used as therapeutic targets and diagnostic markers for glucocorticoid resistance. This study evaluated the missense SNPs of TNF-α, NR3C1, and CYP3A5 to predict their impact on amino acid changes, protein interaction, and functional stability. The protein sequence of dbSNP was obtained and used online in silico method to screen deleterious mutants for the in silico analysis. In the coding regions of TNF-α, NR3C1, and CYP3A5, 14 deleterious mutations were discovered. The protein functional and stability changes in the amino acid between native and mutant energy were identified by analyzing the changes in the hydrogen bonding of these mutants from native, which were all measured using Swiss PDB and PyMOL. F446S and R439K had the highest root-mean-square deviation (RMSD) values among the 14 deleterious mutants. Additionally, the conserved region of amino acid protein interaction was analyzed. This study could aid in the discovery of new detrimental mutations in TNF-α, NR3C1, and CYP3A5, as well as the development of long-term therapy for corticosteroid resistance in several inflammatory diseases. However, more research into the deleterious mutations of the TNF-α, NR3C1, and CYP3A5 genes is needed to determine their role in corticosteroid resistance. MDPI 2022-09-16 /pmc/articles/PMC9496109/ /pubmed/36139147 http://dx.doi.org/10.3390/biom12091307 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ramayanam, Navakanth Raju Manickam, Ranjani Mahalingam, Vijayakumar Thangavel Goh, Khang Wen Ardianto, Chrismawan Ganesan, Poovi Ming, Long Chiau Ganesan, Rajanandh Muhasaparur Functional and Structural Impact of Deleterious Missense Single Nucleotide Polymorphisms in the NR3C1, CYP3A5, and TNF-α Genes: An In Silico Analysis |
title | Functional and Structural Impact of Deleterious Missense Single Nucleotide Polymorphisms in the NR3C1, CYP3A5, and TNF-α Genes: An In Silico Analysis |
title_full | Functional and Structural Impact of Deleterious Missense Single Nucleotide Polymorphisms in the NR3C1, CYP3A5, and TNF-α Genes: An In Silico Analysis |
title_fullStr | Functional and Structural Impact of Deleterious Missense Single Nucleotide Polymorphisms in the NR3C1, CYP3A5, and TNF-α Genes: An In Silico Analysis |
title_full_unstemmed | Functional and Structural Impact of Deleterious Missense Single Nucleotide Polymorphisms in the NR3C1, CYP3A5, and TNF-α Genes: An In Silico Analysis |
title_short | Functional and Structural Impact of Deleterious Missense Single Nucleotide Polymorphisms in the NR3C1, CYP3A5, and TNF-α Genes: An In Silico Analysis |
title_sort | functional and structural impact of deleterious missense single nucleotide polymorphisms in the nr3c1, cyp3a5, and tnf-α genes: an in silico analysis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496109/ https://www.ncbi.nlm.nih.gov/pubmed/36139147 http://dx.doi.org/10.3390/biom12091307 |
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