PMID- 36139147
OWN - NLM
STAT- MEDLINE
DCOM- 20220926
LR  - 20221018
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 12
IP  - 9
DP  - 2022 Sep 16
TI  - Functional and Structural Impact of Deleterious Missense Single Nucleotide 
      Polymorphisms in the NR3C1, CYP3A5, and TNF-alpha Genes: An In Silico Analysis.
LID - 10.3390/biom12091307 [doi]
LID - 1307
AB  - 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-alpha (TNF-alpha), 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-alpha, 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-alpha, 
      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-alpha, 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-alpha, NR3C1, and 
      CYP3A5 genes is needed to determine their role in corticosteroid resistance.
FAU - Ramayanam, Navakanth Raju
AU  - Ramayanam NR
AD  - Department of Pharmacy Practice, SRM College of Pharmacy, SRM Institute of 
      Science and Technology, Kattankulathur 603203, India.
FAU - Manickam, Ranjani
AU  - Manickam R
AD  - SRM-DBT Platform for Advanced Life Science Technologies, SRM Institute of Science 
      and Technology, Kattankulathur 603203, India.
FAU - Mahalingam, Vijayakumar Thangavel
AU  - Mahalingam VT
AD  - Department of Pharmacy Practice, SRM College of Pharmacy, SRM Institute of 
      Science and Technology, Kattankulathur 603203, India.
FAU - Goh, Khang Wen
AU  - Goh KW
AUID- ORCID: 0000-0001-6686-7019
AD  - Faculty of Data Science and Information Technology, INTI International 
      University, Nilai 71800, Malaysia.
FAU - Ardianto, Chrismawan
AU  - Ardianto C
AUID- ORCID: 0000-0003-3713-7900
AD  - Department of Pharmacy Practice, Faculty of Pharmacy, Universitas Airlangga, 
      Surabaya 60115, Indonesia.
FAU - Ganesan, Poovi
AU  - Ganesan P
AD  - Department of Pharmaceutics, College of Pharmacy, Mother Theresa Post Graduate 
      and Research Institute of Health Sciences Gorimedu, Puducherry 605006, India.
FAU - Ming, Long Chiau
AU  - Ming LC
AD  - PAP Rashidah Sa'adatul Bolkiah Institute of Health Sciences, Universiti Brunei 
      Darussalam, Gadong BE1410, Brunei.
FAU - Ganesan, Rajanandh Muhasaparur
AU  - Ganesan RM
AD  - Department of Pharmacy Practice, Sri Ramachandra Faculty of Pharmacy, Sri 
      Ramachandra Institute of Higher Education and Research, Porur, Chennai 600116, 
      India.
LA  - eng
PT  - Journal Article
DEP - 20220916
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (Amino Acids)
RN  - 0 (Glucocorticoids)
RN  - 0 (NR3C1 protein, human)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (TNF protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.14.14.1 (CYP3A5 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
RN  - Glucocorticoid Receptor Deficiency
SB  - IM
MH  - Amino Acids/genetics
MH  - *Cytochrome P-450 CYP3A/genetics
MH  - Glucocorticoids
MH  - Humans
MH  - Metabolism, Inborn Errors
MH  - Mutation, Missense
MH  - *Polymorphism, Single Nucleotide
MH  - *Receptors, Glucocorticoid/genetics
MH  - *Tumor Necrosis Factor-alpha/genetics
PMC - PMC9496109
OTO - NOTNLM
OT  - SNP
OT  - computational study
OT  - glucocorticoid resistance
OT  - missense mutation
OT  - pharmacogenomic
OT  - precision medicine
COIS- The authors declare no conflict of interest.
EDAT- 2022/09/24 06:00
MHDA- 2022/09/28 06:00
PMCR- 2022/09/16
CRDT- 2022/09/23 01:04
PHST- 2022/07/06 00:00 [received]
PHST- 2022/08/24 00:00 [revised]
PHST- 2022/08/31 00:00 [accepted]
PHST- 2022/09/23 01:04 [entrez]
PHST- 2022/09/24 06:00 [pubmed]
PHST- 2022/09/28 06:00 [medline]
PHST- 2022/09/16 00:00 [pmc-release]
AID - biom12091307 [pii]
AID - biomolecules-12-01307 [pii]
AID - 10.3390/biom12091307 [doi]
PST - epublish
SO  - Biomolecules. 2022 Sep 16;12(9):1307. doi: 10.3390/biom12091307.