Aims: Lung adenocarcinoma (LUAD) is the most prominent histological subtype among the lung cancer which is a leading cause in the cancer mortality rate. High mutational and glycolytic rates are the major reported alterations in the lung cancer. Here in our study we are elucidating the structural and functional role of key glycolytic enzyme Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and associated SNPs in LUAD progression.
Materials And Methods: Our gene expression analysis reveals high expression of GAPDH in the LUAD. In silico tools and analysis were used for the identification and characterization of the deleterious SNPs. Molecular Docking and dynamics simulations (MDS) studies characterized the structural consequences of prioritized deleterious mutations.
Key Findings: The sequence based analysis to identify SNPs in GAPDH resulted in 28 deleterious SNPs and 6 SNPs among them showed deleterious and damaging effect. The structural based analysis resulted in 2 stabilizing SNPs of rs ids rs11549328 (D39Y) and rs200102749 (S51Y) in the conserved domain. The IDR and PTM analysis of the GAPDH sequence resulted an IDR region from 191 to 194 positions with an IDR score of 0.511, 0.520, 0.517 and 0.503 with the PTM modifications.
Significance: The identified deleterious SNPs (D39Y and S51Y) fall in the functional and conserved domain of GAPDH. In addition, the existence of PTMs within the IDR region of the GAPDH may contribute to its enhanced glycolytic activity in LUAD. The results of our study provide potential background deleterious mutants the pathological aspect of GAPDH in LUAD progression.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.lfs.2024.123127 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Treatment with 5-MTHF to support the one-carbon cycle can overcome the deleterious impact of a triple SNP mutation in the male partner's MTHFR gene for a couple with a history of repeated miscarriage.
J Assist Reprod Genet
January 2025
Laboratoire Clément, Avenue d'Eylau, 75016, Paris, France.
A couple presenting with more than 3 years' history of infertility and three miscarriages was tested for serum homocysteine levels and for the two principal MTHFR SNPs: 677C < T and 1298A < C, as per our general policy for patients with infertility of long duration. The woman was found to be wild type for both MTHFR SNPs with a serum homocysteine 10.5 µM, slightly higher than our accepted normal value of 8.
View Article and Find Full Text PDFPrediction the functional impacts of highly deleterious non-synonymous variants of gene.
Mol Biol Res Commun
January 2025
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Article Synopsis
- TSGA10 is a protein involved in spermatogenesis and associated with various cancers, where mutations can lead to infertility and abnormal expression in tumors.
- Research identifies the impact of specific non-synonymous SNPs (nsSNPs) on TSGA10's structure and function using multiple predictive in-silico tools before conducting expensive lab experiments.
- The study highlights 15 significantly damaging amino acid changes, particularly in regions linked to interactions with other proteins, suggesting these mutations can greatly affect TSGA10's role in infertility and cancer research.
Pharmacogenomic landscape of the Thai population from genome sequencing of 949 individuals.
Sci Rep
December 2024
National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand.
Inter-individual variability in drug responses is significantly influenced by genetic factors, underscoring the importance of population-specific pharmacogenomic studies to optimize clinical outcomes. In this study, we analyzed whole genome sequencing data from 949 unrelated Thai individuals and conducted an in-depth analysis of 3239 genes involved in drug pharmacokinetics, pharmacodynamics, or immune-mediated adverse drug reactions. We identified 43 single nucleotide polymorphisms (SNPs), 134 diplotypes, and 15 human leukocyte antigen (HLA) alleles, all with moderate to high clinical significance.
View Article and Find Full Text PDFComprehensive characterization of high-risk coding and non-coding single nucleotide polymorphisms of human CXCR4 gene.
PLoS One
December 2024
Infection Biology Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh.
CXCR4, a chemokine receptor known as Fusin or CD184, spans the outer membrane of various human cells, including leukocytes. This receptor is essential for HIV infection as well as for many vital cellular processes and is implicated to be associated with multiple pathologies, including cancers. This study employs various computational tools to investigate the molecular effects of disease-vulnerable germ-line missense and non-coding SNPs of the CXCR4 gene.
View Article and Find Full Text PDFPathogenic single nucleotide polymorphisms in RhoA gene: Insights into structural and functional impacts on RhoA-PLD1 interaction through molecular dynamics simulation.
Curr Res Struct Biol
November 2024
Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh.
Molecular switches serve as key regulators of biological systems by acting as one of the crucial driving forces in the initiation of signal transduction pathway cascades. The Ras homolog gene family member A (RhoA) is one of the molecular switches that binds with GTP in order to cycle between an active GTP-bound state and an inactive GDP-bound state. Any aberrance in control over this circuit, particularly due to any perturbation in switching, leads to the development of different pathogenicity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!