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...

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Main Authors: Navakanth Raju Ramayanam, -, Ranjani Manickam, -, Vijayakumar Thangavel Mahalingam, -, Khang Wen Goh, -, Chrismawan Ardianto, -, Poovi Ganesan, -, Long Chiau Ming, -, Rajanandh Muhasaparur Ganesan, -
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Language:English
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Published: Multidisciplinary Digital Publishing Institute (MDPI) 2022
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Online Access:https://repository.unair.ac.id/125190/1/Artikel%20C-12.pdf
https://repository.unair.ac.id/125190/2/%28C-12%29%20Kualitas%20Karil.pdf
https://repository.unair.ac.id/125190/3/Similarity%20C-12.pdf
https://repository.unair.ac.id/125190/4/Bukti%20Korespondensi%20C-12.pdf
https://repository.unair.ac.id/125190/
https://www.mdpi.com/2218-273X/12/9/1307
https://doi.org/10.3390/biom12091307
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spelling id-langga.1251902023-04-28T00:39:59Z https://repository.unair.ac.id/125190/ Functional and Structural Impact of Deleterious Missense Single Nucleotide Polymorphisms in the NR3C1, CYP3A5, and TNF-α Genes: An In Silico Analysis Navakanth Raju Ramayanam, - Ranjani Manickam, - Vijayakumar Thangavel Mahalingam, - Khang Wen Goh, - Chrismawan Ardianto, - Poovi Ganesan, - Long Chiau Ming, - Rajanandh Muhasaparur Ganesan, - R Medicine RS Pharmacy and materia medica RS1-441 Pharmacy and materia medica RS200-201 Pharmaceutical dosage forms 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. Multidisciplinary Digital Publishing Institute (MDPI) 2022-09-16 Article PeerReviewed text en https://repository.unair.ac.id/125190/1/Artikel%20C-12.pdf text en https://repository.unair.ac.id/125190/2/%28C-12%29%20Kualitas%20Karil.pdf text en https://repository.unair.ac.id/125190/3/Similarity%20C-12.pdf text en https://repository.unair.ac.id/125190/4/Bukti%20Korespondensi%20C-12.pdf Navakanth Raju Ramayanam, - and Ranjani Manickam, - and Vijayakumar Thangavel Mahalingam, - and Khang Wen Goh, - and Chrismawan Ardianto, - and Poovi Ganesan, - and Long Chiau Ming, - and Rajanandh Muhasaparur Ganesan, - (2022) Functional and Structural Impact of Deleterious Missense Single Nucleotide Polymorphisms in the NR3C1, CYP3A5, and TNF-α Genes: An In Silico Analysis. Biomolecules, 12 (9). pp. 1-18. ISSN 2218-273X https://www.mdpi.com/2218-273X/12/9/1307 https://doi.org/10.3390/biom12091307
institution Universitas Airlangga
building Universitas Airlangga Library
continent Asia
country Indonesia
Indonesia
content_provider Universitas Airlangga Library
collection UNAIR Repository
language English
English
English
English
topic R Medicine
RS Pharmacy and materia medica
RS1-441 Pharmacy and materia medica
RS200-201 Pharmaceutical dosage forms
spellingShingle R Medicine
RS Pharmacy and materia medica
RS1-441 Pharmacy and materia medica
RS200-201 Pharmaceutical dosage forms
Navakanth Raju Ramayanam, -
Ranjani Manickam, -
Vijayakumar Thangavel Mahalingam, -
Khang Wen Goh, -
Chrismawan Ardianto, -
Poovi Ganesan, -
Long Chiau Ming, -
Rajanandh Muhasaparur Ganesan, -
Functional and Structural Impact of Deleterious Missense Single Nucleotide Polymorphisms in the NR3C1, CYP3A5, and TNF-α Genes: An In Silico Analysis
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 Article
PeerReviewed
author Navakanth Raju Ramayanam, -
Ranjani Manickam, -
Vijayakumar Thangavel Mahalingam, -
Khang Wen Goh, -
Chrismawan Ardianto, -
Poovi Ganesan, -
Long Chiau Ming, -
Rajanandh Muhasaparur Ganesan, -
author_facet Navakanth Raju Ramayanam, -
Ranjani Manickam, -
Vijayakumar Thangavel Mahalingam, -
Khang Wen Goh, -
Chrismawan Ardianto, -
Poovi Ganesan, -
Long Chiau Ming, -
Rajanandh Muhasaparur Ganesan, -
author_sort Navakanth Raju Ramayanam, -
title 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_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_sort functional and structural impact of deleterious missense single nucleotide polymorphisms in the nr3c1, cyp3a5, and tnf-α genes: an in silico analysis
publisher Multidisciplinary Digital Publishing Institute (MDPI)
publishDate 2022
url https://repository.unair.ac.id/125190/1/Artikel%20C-12.pdf
https://repository.unair.ac.id/125190/2/%28C-12%29%20Kualitas%20Karil.pdf
https://repository.unair.ac.id/125190/3/Similarity%20C-12.pdf
https://repository.unair.ac.id/125190/4/Bukti%20Korespondensi%20C-12.pdf
https://repository.unair.ac.id/125190/
https://www.mdpi.com/2218-273X/12/9/1307
https://doi.org/10.3390/biom12091307
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