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Your search keyword '"Chatterjee, Sompriya"' showing total 15 results
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15 results on '"Chatterjee, Sompriya"'

11. Histidine Tautomerism Driving Human Islet Amyloid Polypeptide Aggregation in the Early Stages of Diabetes Mellitus Progression: Insight at the Atomistic Level.

Author

Salimi, Abbas, Chatterjee, Sompriya, and Yong Lee, Jin

Subjects
*AMYLIN, *MOLECULAR dynamics, *HISTIDINE, *DIABETES, *TYPE 2 diabetes, *ISOMERS
Abstract

Early oligomerization of human islet amyloid polypeptide (hIAPP), which is accountable for β‐cell death, has been implicated in the progression of type 2 diabetes mellitus. Some researches have shown the connection between hIAPP and Alzheimer's disease as well. However, the mechanism of peptide accumulation and associated cytotoxicity remains unclear. Due to the unique properties and significant role of histidine in protein sequences, here for the first time, the tautomeric effect of histidine at the early stages of amylin misfolding was investigated via molecular dynamics simulations. Considering Tau and Pi tautomeric forms of histidine (Tau and Pi tautomers are denoted as ϵ and δ, respectively), simulations were performed on two possible isomers of amylin. Our analysis revealed a higher probability of transient α‐helix generation in the δ isomer in monomeric form. In dimeric forms, the δδ and δϵ conformations showed an elevated amount of α‐helix and lower coil in comparison to the ϵϵ dimer. Due to the significant role of α‐helix in membrane disruption and transition to β‐sheet structure, these results may imply a noticeable contribution of the δ isomer and the δδ and δϵ dimers rather than ϵ and ϵϵ conformations in the early stages of diabetes initiation. Our results may aid in elucidating the hIAPP self‐association process in the etiology of amyloidosis. [ABSTRACT FROM AUTHOR]

Published
2021
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12. Insights into amyotrophic lateral sclerosis linked Pro525Arg mutation in the fused in sarcoma protein through in silicoanalysis and molecular dynamics simulation

Author

Chatterjee, Sompriya, Salimi, Abbas, and Lee, Jin Yong

Abstract

AbstractA novel heterozygous mutation, Pro525Arg (P525R) in the Fused in Sarcoma (FUS) protein is predominant in young adult females with familial amyotrophic lateral sclerosis (fALS). Investigation of the biophysical characteristics of this mutation through analysis of protein conformation could provide insights into the pathogenic mechanism of amyotrophic lateral sclerosis (ALS). Here, several computational prediction tools were applied to investigate the effect of P525R on the stability, flexibility, and function of FUS. Conservation and biochemical analyses showed that P525 is highly conserved; the mutation of proline to arginine at position 525 in FUS results in a notable increase in molecular weight, number of hydrogen bonds, and loss of hydrophobicity. By performing electrostatic potential, intra-protein interaction, and binding affinity analyses, we found increased electrostatic potential charge in the mutant protein and fewer hydrophobic interactions than the wild-type structure. Binding affinity of the FUS nuclear localization signal (NLS) mutant for transportin (Trn1) was also decreased compared to wild-type. Our molecular dynamics (MD) simulation results highlighted the exchange between hydrophobic and hydrophilic residues from the core to the surface in the mutant structure; also, upon P525R mutation, FUS became less stable, less flexible and more compact and rigid. Overall, this study demonstrated that the Pro525Arg mutation significantly alters the structure and conformation of FUS through loss of nuclear function, thereby likely contributing to its accumulation in the cytoplasm, which has been implicated in the pathogenesis of fALS. Our study can potentially aid in the design of drugs for FUS-associated neurodegenerative diseases.

Published
2021
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15. Intrinsic Origin of Tau Protein Aggregation: Effects of Histidine Tautomerism on Tau 267-312 Monomer.

Author

Chatterjee S, Salimi A, and Lee JY

Subjects
Amyloid beta-Peptides, Molecular Dynamics Simulation, Protein Aggregates, Protein Conformation, beta-Strand, Histidine, tau Proteins
Abstract

Histidine tautomerism is considered a crucial component that affects the constitutional and accumulation characteristics of the tau 267-312 monomer in the neutral condition, which are connected with the pathobiology of Alzheimer's disease (AD). Interpreting the organizational characteristics and accumulation procedure is a challenging task because two tautomeric conformations (the N ε -H or N δ -H tautomer) can occur in the open neutral condition. In the current work, replica-exchange molecular dynamics (REMD) simulations were performed to investigate the structural properties of the tau 267-312 monomer considering the histidine tautomeric effect. Based on the simulation outcomes, the histidine 268 (H268) (δ)-H299 (δ) (δδ) isomer had the highest β-sheet content with a value of 26.2%, which acquires a sheet-governing toxic conformer with the first abundant conformational state of 22.6%. In addition, δδ displayed notable antiparallel β-sheets between lysine 8 (K8)-asparagine 13 (N13) and valine 40 (V40)-tyrosine 44 (Y44) as well as between K32-H33 and V40-Y44 (β-meander supersecondary structure), indicating this tautomeric isomer may exist to stimulate tau oligomerization. Furthermore, H299 was found to play an essential role in the structural stabilization of the δδ isomer compared with H268. The present research will aid in obtaining insight into the organizational and accumulation properties of tau protein in the presence of histidine tautomerism to control AD.

Published
2020
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