scholarly journals Molecular Modelling of nsSNPs in GABRA2 Gene in Epilepsy and Study of Their Impact On Structure and Stability of GABRA2 Protein

2021 ◽  
Author(s):  
Zehra Agha ◽  
Maleeha Azam ◽  
Bushra Faryal
Keyword(s):  
Protein Structure ◽  
Focal Epilepsy ◽  
Missense Variant ◽  
Epilepsy Syndrome ◽  
Conservation Analysis ◽  
Structure And Stability ◽  
Bioinformatic Tools ◽  
Coding Variants ◽  
String Databases ◽  
The Impact

Abstract Epilepsy is a neurological condition characterized by abrupt, unprovoked, and recurrent seizures that are unpredictable in frequency. The objective of this analysis was to identify novel non-synonymous polymorphisms in the GABRA2 gene and determine their effect on protein structure and stability. Most pathogenic/deleterious nsSNPs were predicted using six different bioinformatic tools. Mutpred2, Mupro was used to check the impact of identified nsSNPS on protein structure and stability. The pathogenic score of SNPs was predicted using the FATHMM tool. The CONSURF webserver was used for conservation analysis of pathogenic SNPs.3-D structure of the protein was realized using SWISS-MODEL and residue position in protein visualized by Lite Mol. GeneMANIA and STRING databases were used to predict the function of interlinked gene interactions. Out of 228 nsSNPs retrieved from the dbSNP database, we identified a novel missense variant, F285S (rs41310789), as most deleterious and its possible association with epilepsy syndrome focal epilepsy. Stability and conservation analysis results interpret rs41310789 present in evolutionarily conserved regions of a gene and affect its structure. This analysis provides information regarding the impact of nsSNPs that might affect the structure and activity of GABRA2 protein. Thus, these coding variants should be taken into scrutiny while genetic screening of epileptic patients.

scholarly journals Molecular Modelling and Dynamics Study of nsSNP in STXBP1 Gene in Early Infantile Epileptic Encephalopathy Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Krami Al Mehdi ◽  
Benhnini Fouad ◽  
Elkarhat Zouhair ◽  
Belkady Boutaina ◽  
Naasse Yassine ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Protein Structure ◽  
High Risk ◽  
Hydrophobic Interactions ◽  
Epileptic Encephalopathy ◽  
Snare Complex ◽  
Dynamics Simulation ◽  
Conservation Analysis ◽  
The Impact ◽  
Different Levels

Early Infantile Epileptic Encephalopathy (known as Ohtahara Syndrome) is one of the most severe and earliest forms of epilepsy, characterized by early seizures onset. It affects newborns and children between two and six years old. Among the genes that have been associated with early infantile epileptic encephalopathy, the STXBP1 gene, which encodes the Syntaxin binding protein1a that is involved in SNARE complex formation, contributes to synaptic vesicles exocytosis. The aim of this study was to identify the most pathogenic polymorphisms of STXBP1 gene and determine their impact on the structure and stability of Stxbp1 protein. The high-risk nonsynonymous single nucleotide polymorphisms (nsSNPs) in the STXBP1 gene were predicted using 13 bioinformatics tools. The conservation analysis was realized by CONSURF web server. The analysis of the impact of the pathogenic SNPs on the structure of Stxbp1 protein was realized using YASARA software, and the molecular dynamics simulation was performed using GROMACS software. Out of 245 nsSNPs, we identified 11 (S42P, H103D R190W, R235G, D238E, L256P, P335S, C354Y, L365V, R406C, and G544D) as deleterious using in silico prediction tools. Conservation analysis results revealed that all these nsSNPs were located in conserved regions. The comparison of the hydrogen and hydrophobic interactions in the wild type Stxbp1 structure and its mutant forms showed that all these nsSNPs affect the protein structure on different levels. The molecular dynamics simulations revealed that the total of nsSNPs affect the protein stability, residual fluctuation, and the compaction at different levels. This study provides helpful information on high risk nsSNPs that may affect the Stxbp1 protein structure and function. Thus, these variants should be taken into consideration during the genetic screening of patients suffering from early infantile epileptic encephalopathy.

scholarly journals A comparative study on the extraction effects of common agents on collagen-based binders in mural paintings

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jianghao Du ◽  
Zhanyun Zhu ◽  
Junchang Yang ◽  
Jia Wang ◽  
Xiaotong Jiang
Keyword(s):  
Protein Structure ◽  
Comparative Study ◽  
Protein Extraction ◽  
Guanidine Hydrochloride ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Extraction Process ◽  
Ultraviolet Absorption Spectrum ◽  
Mural Paintings ◽  
The Impact

AbstractIn this paper, a comparative study was conducted on the extraction effects of six agents for collagen-based mural painting binders. These agents were used to extract the residual proteins in the non-aged and thermal aged samples. The protein extraction efficiencies of different extracting agents were quantitatively determined by bicinchoninic acid (BCA) method, and then processed by multivariate analysis of variance (MANOVA). The impact of the extraction process on the protein structure was characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), ultraviolet absorption spectrum (UV) and circular dichroism (CD). The results showed that, for both non-aged and aged samples, the extraction efficiency of 2 M guanidine hydrochloride (GuHCl) was significantly higher than the other five agents, with less damage to the protein structure during the extraction process.

scholarly journals Codon harmonization reduces amino acid misincorporation in bacterially expressed P. falciparum proteins and improves their immunogenicity

AMB Express ◽  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Neeraja Punde ◽  
Jennifer Kooken ◽  
Dagmar Leary ◽  
Patricia M. Legler ◽  
Evelina Angov
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Codon Usage ◽  
Dna Sequences ◽  
Structural Integrity ◽  
Host Cells ◽  
Loss Of Function ◽  
Species Specific ◽  
And Function ◽  
The Impact

Abstract Codon usage frequency influences protein structure and function. The frequency with which codons are used potentially impacts primary, secondary and tertiary protein structure. Poor expression, loss of function, insolubility, or truncation can result from species-specific differences in codon usage. “Codon harmonization” more closely aligns native codon usage frequencies with those of the expression host particularly within putative inter-domain segments where slower rates of translation may play a role in protein folding. Heterologous expression of Plasmodium falciparum genes in Escherichia coli has been a challenge due to their AT-rich codon bias and the highly repetitive DNA sequences. Here, codon harmonization was applied to the malarial antigen, CelTOS (Cell-traversal protein for ookinetes and sporozoites). CelTOS is a highly conserved P. falciparum protein involved in cellular traversal through mosquito and vertebrate host cells. It reversibly refolds after thermal denaturation making it a desirable malarial vaccine candidate. Protein expressed in E. coli from a codon harmonized sequence of P. falciparum CelTOS (CH-PfCelTOS) was compared with protein expressed from the native codon sequence (N-PfCelTOS) to assess the impact of codon usage on protein expression levels, solubility, yield, stability, structural integrity, recognition with CelTOS-specific mAbs and immunogenicity in mice. While the translated proteins were expected to be identical, the translated products produced from the codon-harmonized sequence differed in helical content and showed a smaller distribution of polypeptides in mass spectra indicating lower heterogeneity of the codon harmonized version and fewer amino acid misincorporations. Substitutions of hydrophobic-to-hydrophobic amino acid were observed more commonly than any other. CH-PfCelTOS induced significantly higher antibody levels compared with N-PfCelTOS; however, no significant differences in either IFN-γ or IL-4 cellular responses were detected between the two antigens.

Effect of conserved intersubunit amino acid substitutions on Hfq protein structure and stability

2014 ◽  
Vol 79 (5) ◽  
pp. 469-477 ◽  
Author(s):  
V. N. Murina ◽  
B. S. Melnik ◽  
V. V. Filimonov ◽  
M. Ühlein ◽  
M. S. Weiss ◽  
...  
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Amino Acid Substitutions ◽  
Structure And Stability

scholarly journals NGS Analysis for Molecular Diagnosis of Retinitis Pigmentosa (RP): Detection of a Novel Variant in PRPH2 Gene

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 792 ◽  
Author(s):  
Claudia Strafella ◽  
Valerio Caputo ◽  
Giulia Pagliaroli ◽  
Nicola Iozzo ◽  
Giulia Campoli ◽  
...  
Keyword(s):  
Molecular Diagnosis ◽  
Missense Variant ◽  
Bioinformatic Analysis ◽  
Protein Activity ◽  
Helical Structures ◽  
Retinal Dystrophies ◽  
Novel Variant ◽  
History Of ◽  
The Impact ◽  
Variant Protein

This work describes the application of NGS for molecular diagnosis of RP in a family with a history of severe hypovision. In particular, the proband received a clinical diagnosis of RP on the basis of medical, instrumental examinations and his family history. The proband was subjected to NGS, utilizing a customized panel including 24 genes associated with RP and other retinal dystrophies. The NGS analysis revealed a novel missense variant (c.668T > A, I223N) in PRPH2 gene, which was investigated by segregation and bioinformatic analysis. The variant is located in the D2 loop domain of PRPH2, which is critical for protein activity. Bioinformatic analysis described the c.668T > A as a likely pathogenic variant. Moreover, a 3D model prediction was performed to better characterize the impact of the variant on the protein, reporting a disruption of the α-helical structures. As a result, the variant protein showed a substantially different conformation with respect to the wild-type PRPH2. The identified variant may therefore affect the oligomerization ability of the D2 loop and, ultimately, hamper PRPH2 proper functioning and localization. In conclusion, PRPH2_c.668T > A provided a molecular explanation of RP symptomatology, highlighting the clinical utility of NGS panels to facilitate genotype–phenotype correlations.

scholarly journals The Impact of Coilin Nonsynonymous SNP Variants E121K and V145I on Cell Growth and Cajal Body Formation: The First Characterization

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 895
Author(s):  
Yue Yao ◽  
Heng Wee Tan ◽  
Zhan-Ling Liang ◽  
Gao-Qi Wu ◽  
Yan-Ming Xu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Structure ◽  
Cell Growth ◽  
Subcellular Localization ◽  
Structure Prediction ◽  
Bioinformatic Analysis ◽  
Survival Motor Neuron ◽  
Cajal Body ◽  
Survival Motor Neuron Protein ◽  
The Impact

Coilin is the main component of Cajal body (CB), a membraneless organelle that is involved in the biogenesis of ribonucleoproteins and telomerase, cell cycle, and cell growth. The disruption of CBs is linked to neurodegenerative diseases and potentially cancers. The coilin gene (COIL) contains two nonsynonymous SNPs: rs116022828 (E121K) and rs61731978 (V145I). Here, we investigated for the first time the functional impacts of these coilin SNPs on CB formation, coilin subcellular localization, microtubule formation, cell growth, and coilin expression and protein structure. We revealed that both E121K and V145I mutants could disrupt CB formation and result in various patterns of subcellular localization with survival motor neuron protein. Noteworthy, many of the E121K cells showed nucleolar coilin accumulation. The microtubule regrowth and cell cycle assays indicated that the E121K cells appeared to be trapped in the S and G2/M phases of cell cycle, resulting in reduced cell proliferation. In silico protein structure prediction suggested that the E121K mutation caused greater destabilization on the coilin structure than the V145I mutation. Additionally, clinical bioinformatic analysis indicated that coilin expression levels could be a risk factor for cancer, depending on the cancer types and races.

Altered Structural and Functional Feature of Striato-Cortical Circuit in Benign Epilepsy with Centrotemporal Spikes

2015 ◽  
Vol 25 (06) ◽  
pp. 1550027 ◽  
Author(s):  
Cheng Luo ◽  
Yaodan Zhang ◽  
Weifang Cao ◽  
Yue Huang ◽  
Fei Yang ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Focal Epilepsy ◽  
Brain Morphology ◽  
Brain Maturation ◽  
Epilepsy Syndrome ◽  
Healthy Children ◽  
Functional Feature ◽  
Motor Network ◽  
Cortical Circuit ◽  
Benign Epilepsy

Benign epilepsy with centrotemporal spikes (BECT) is the most common form of childhood idiopathic focal epilepsy syndrome. We investigated quantitative evidence regarding brain morphology and functional connectivity features to provide insight into the neuroanatomical foundation of this disorder, using high resolution T1-weighted magnetic resonance imaging (MRI) and resting state functional MRI in 21 patients with BECT and in 20 healthy children. The functional connectivity analysis, seeded at the regions with altered gray-matter (GM) volume in voxel-based morphometry (VBM) analysis, was further performed. Then, the observed structural and functional alteration were investigated for their association with the clinical and behavior manifestations. The increased GM volume in the striatum and fronto-temporo-parietal cortex (striato-cortical circuit) was observed in BECT. The decreased connections were found among the motor network and frontostriatal loop, and between the default mode network (DMN) and language regions. Additionally, the GM of striatum was negatively correlated with age at epilepsy onset. The current observations may contribute to the understanding of the altered structural and functional feature of striato-cortical circuit in patients with BECT. The findings also implied alterations of the motor network and DMN, which were associated with the epileptic activity in patients with BECT. This further suggested that the onset of BECT might have enduring structural and functional effects on brain maturation.

Facial Dysmorphisms, Macrodontia, Focal Epilepsy, and Thinning of the Corpus Callosum: A Rare Mild Form of Kabuki Syndrome

2020 ◽  
Author(s):  
Valentina Bruni ◽  
Cristina Scozzafava ◽  
Maria Gnazzo ◽  
Francesca Parisi ◽  
Simona Sestito ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Focal Epilepsy ◽  
Missense Variant ◽  
Postnatal Growth ◽  
Facial Features ◽  
Kabuki Syndrome ◽  
Genetic Condition ◽  
Atypical Form ◽  
Skeletal Defects ◽  
Immunological Abnormalities

AbstractKabuki syndrome (KS) is a rare genetic condition with multiple congenital abnormalities and developmental delay. The cardinal manifestations of KS include characteristic facial features, intellectual disability, skeletal defects, dermatoglyphic abnormalities, and postnatal growth deficiencies. Cardiac and urological malformations are commonly present in patient with KS, as well as language deficits and immunological abnormalities. Here, we report a case of a child with an atypical form of KS, associated with macrodontia, corpus callosum dysmorphism, focal epilepsy responsive to antiepileptic treatment, and a novel KMT2D gene missense variant, c.2413C > T, never reported to date.

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