Nandini Sarkar | National Institute of Technology Rourkela (original) (raw)

Papers by Nandini Sarkar

3 Biotech

Amyloidogenesis is the inherent ability of proteins to change their conformation from native stat... more Amyloidogenesis is the inherent ability of proteins to change their conformation from native state to cross β-sheet rich fibrillar structures called amyloids which result in a wide range of diseases like Parkinson's disease, Alzheimer's disease, Finnish familial amyloidosis, ATTR amyloidosis, British and Danish dementia, etc. COVID-19, on the other hand is seen to have many similarities in symptoms with other amyloidogenic diseases and the overlap of these morbidities and symptoms led to the proposition whether SARS-CoV-2 proteins are undergoing amyloidogenesis and whether it is resulting in or aggravating amyloidogenesis of any human host protein. Thus the SARS-CoV-2 proteins in infected cells, i.e., Spike (S) protein, Nucleocapsid (N) protein, and Envelope (E) protein were tested via different machinery and amyloidogenesis in them were proven. In this review, we will analyze the pathway of amyloid formation in S-protein, N-protein, E-protein along with the effect that SARS-CoV-2 is creating on various host proteins leading to the unexpected onset of many morbidities like COVID-induced Acute Respiratory Distress Syndrome (ARDS), Parkinsonism in young COVID patients, formation of fibrin microthrombi in heart, etc., and their future implications.

Journal of Molecular Structure

bioRxiv, 2022

Alzheimer’s Disease is a neurodegenerative disease for which no cure is available at present. The... more Alzheimer’s Disease is a neurodegenerative disease for which no cure is available at present. The presence of amyloid plaques in the extracellular space of neural cells is the key feature of this fatal disease. Amyloid-Beta (Aβ) is a 40-42 amino acid peptide and the main component of amyloid plaques. This peptide is produced by the proteolysis of Amyloid Precursor Protein by presenilin. Deposition of 42 residual Aβ peptides forms fibrils structure, leading to disruption of neuron synaptic transmission, inducing neural cell toxicity, ultimately leading to neuron death. To modulate the amyloidosis of Aβ peptides, various novel peptides have been investigated via molecular docking and molecular dynamic simulation studies. The sequence-based peptides were designed and investigated for their interaction with Aβ42 monomer and fibril using the molecular docking method, and their influence on the structural stability of target proteins was studied using molecular simulations. According to t...

Advances in Natural Sciences: Nanoscience and Nanotechnology, 2022

In this work, the core carbon nanoparticles (BM CNs) and polyethylene glycol 400 (PEG400)-capped ... more In this work, the core carbon nanoparticles (BM CNs) and polyethylene glycol 400 (PEG400)-capped BM CNs were synthesised from Butea monosperma flower extract via the facile direct heating method. They were investigated for their intriguing properties and in vitro antioxidation activity in comparison with Carica papaya seed (CPS) extract via DPPH assay. The CNs were characterised by DLS, XRD, HR-TEM, TGA, FT-IR, UV–vis spectral analysis and quantum yield measurement. The PEGylated CNs demonstrated decent quantum yield, favourable size, and turbostratic carbon phase apart from better stability and dispersion nature as compared to the uncapped entity. The mildly stable uncapped sample with zeta potential −17.9 mV featured its extensively aggregated form, unlike the capped sample with −23.0 mV zeta potential, which sheds light on its enhanced stability by PEG400. Antiradical capacities of the CNs in comparison with CPS extract demonstrated the PEG400-bound nanomaterial of its superior a...

Protein & Peptide Letters, 2022

: Amyloid fibrils are highly stable protein fibrillar aggregates believed to be involved in vario... more : Amyloid fibrils are highly stable protein fibrillar aggregates believed to be involved in various neurodegenerative diseases, which include Alzheimer’s disease, Parkinson’s disease, and prion diseases. Inhibiting the aggregation process is a potential strategy to prevent diseases caused by amyloid formation. In this regard, nanoparticles have emerged as promising candidates owing to their unique physical/chemical properties of small size, large surface area, biocompatibility, biodegradability, non-toxicity, and ease of functionalization. Human Serum Albumin (HSA) is a soluble multidomain monomeric protein that interacts with various ligands and hormones, aiding in their transport, distribution, metabolism in the circulatory system, and also plays a vital role in extracellular fluid volume stabilization. Under certain in vitro conditions, HSA has been reported to undergo conformational changes leading to fibril formation and hence acts as a suitable model for studying amyloidogenesis. In this review, we have explored the effects of various nanoparticles on HSA aggregation and their mechanism of action. The study will throw light on the mechanistic details of nanoparticle-mediated amyloid modulation, which will help in the development of effective therapeutics against amyloidosis.

Archives of Biochemistry and Biophysics, 2021

All proteins have the inherent ability to undergo transformation from their native structure to a... more All proteins have the inherent ability to undergo transformation from their native structure to a β sheet rich fibrillar structure, called amyloid when subjected to specific conditions. Proteins with a high propensity to form amyloid fibrils have been implicated in a variety of disorders like Alzheimer's disease, Parkinson's disease, Type II diabetes, Amyotrophic Lateral Sclerosis (ALS) and prion diseases. Among the various critical factors that modulate the process of amyloid formation, disulfide bonds have been identified as one of the key determinants of amyloid propensity in proteins. Studies have shown that intra-molecular disulfide bonds impart stability to the native structure of a protein and decrease the tendency for amyloid aggregation, whereas intermolecular disulfide bonds aid in the process of aggregation. In this review, we will analyze the varying effects of both intra as well as inter-molecular disulfide bonds have on the amyloid aggregation propensities of few proteins associated with amyloid disorders.

Current Proteomics, 2021

Background: Amyloids are a class of ordered protein aggregates which have been implicated in the ... more Background: Amyloids are a class of ordered protein aggregates which have been implicated in the onset of several degenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Type II diabetes, and so on. Despite extensive research, the exact mechanism and the driving factors for the amyloidogenesis process remain elusive. Identifying molecules which can effectively inhibit and/or disaggregate the fibrils may be one effective therapeutic strategy against amyloidosis. Objectives: In the current study, few hydroxy-benzoic phytochemicals were selected to study their effects on the formation as well as disaggregation of Hen Egg-White Lysozyme (HEWL) amyloids, namely gallic acid, syringic acid, vanillic acid, and iso-vanillic acid. Method: Amyloidogenesis was monitored using methods like the thioflavin T assay, Field Emission Scanning Electron Microscopy (FESEM), and dynamic light scattering (DLS) studies. Further protein conformational changes were monitored using methods lik...

Archives of Biochemistry and Biophysics, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Protein & Peptide Letters, 2019

Amyloids are highly ordered beta sheet rich stable protein aggregates, which have been found to p... more Amyloids are highly ordered beta sheet rich stable protein aggregates, which have been found to play a significant role in the onset of several degenerative diseases such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Type II diabetes mellitus and so on. Aggregation of proteins leading to amyloid fibril formation via intermediate(s), is thought to be a nucleated condensation polymerization process associated with many pathological conditions. There has been extensive research to identify inhibitors of these disease oriented aggregation processes. In recent times, quantum dots, with their unique physico-chemical properties have grabbed the attention of scientific community due to its applications in medical sciences. Quantum dots are nano-particles usually made of semiconductor materials which emit fluorescence upon radiation. The wavelength of fluorescence emission varies with changes in size of quantum dots. Several studies have reported significant inhibitory e...

Colloids and Surfaces B: Biointerfaces, 2019

Amyloid fibrils are the hallmarks of neurodegenerative diseases like Alzheimer's, Parkinson's and... more Amyloid fibrils are the hallmarks of neurodegenerative diseases like Alzheimer's, Parkinson's and other proteopathies. Inhibition of fibrillation is a potential strategy to check the progress of amyloid associated diseases and further allied deterioration. In this study, we have synthesized proline functionalized gold nanoparticles (Pro-AuNPs) and scrutinized its antifibrillation property towards Hen Egg White Lysozyme (HEWL) aggregation. Pro-AuNPs were characterized using various biophysical methods like ultraviolet-visible spectroscopy, fourier transform infra-red spectroscopy, zeta potential measurement, dynamic light scattering and transmission electron microscopy. The effect of Pro-AuNPs on HEWL fibrillation was analyzed employing thioflavin T (ThT) and 8-Anilino-1-naphthalenesulfonic acid (ANS) assays. The kinetics of HEWL exhibited a typical sigmoidal nature of protein aggregation and was fitted to Boltzmann model. HEWL in the presence of bare gold nanoparticles (bAuNPs) exhibited similar aggregation kinetics as HEWL alone. However, HEWL fibrillation substantially reduced upon co-incubation with proline and Pro-AuNPs, and two slightly different intermediate species were formed with these two systems as predicted by CD spectroscopy. TEM images also supported the above observation displaying different morphological states of HEWL aggregates in the presence of proline and Pro-AuNPs. Using computational methods, the nature of interaction of HEWL and proline was found to be hydrogen bonding and hydrophobic interaction in multiple amyloidogenic regions. These interactions inhibited the formation of prefibrils (β-sheet rich intermediates) and also found to disintegrate fibrils. Furthermore, HEWL-Pro-AuNPs system resulted HEWL adsorption through hydrophobic patches, which blocked the intermolecular βsheet formation. The present study successfully established Pro-AuNPs as a potential inhibitor of HEWL aggregation.

Biomedicines, 2017

Protein amyloids are characterized by aggregates that usually consist of fibres containing misfol... more Protein amyloids are characterized by aggregates that usually consist of fibres containing misfolded proteins and having a cross β-sheet conformation. These aggregates can eventually lead to several degenerative diseases like Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Huntington’s disease and Parkinson’s disease. The present study describes the effect of chemically synthesized polyvinylpyrrolidone (PVP)-conjugated gold nanoparticles (PVP-AuNps) on hen egg white lysozyme (HEWL) amyloids. The synthesized nanoparticles have been characterized using various biophysical techniques like Ultraviolet-Visible (UV-Vis) Spectroscopy, Transmission electron microscopy (TEM), X-ray diffraction (XRD) analysis, dynamic light scattering (DLS), zeta-potential measurement and Fourier transform infrared spectroscopy (FTIR). The aggregation studies showed that PVP acts as a partial inhibitor of HEWL amyloidogenesis. However, when conjugated to gold nanoparticle surface, it leads to comple...

The Protein Journal, 2017

Current Trends in Biotechnology and …, 2008

Trypanothione synthetase(TryS) is an important enzyme for survival of Leishmania; thus an importa... more Trypanothione synthetase(TryS) is an important enzyme for survival of Leishmania; thus an important target for structure based drug design against leishmaniasis. We have constructed three-dimensional structure of the TryS of Leishmania infantum by homology modeling with acceptable ...

Biopolymer-Based Formulations, 2020

Protein & Peptide Letters

Background: Fibroblast growth Factor Homologous Factors (FHFs) belong to a subclass of Fibroblast... more Background: Fibroblast growth Factor Homologous Factors (FHFs) belong to a subclass of Fibroblast Growth Factor (FGF) family owing to their high sequence and structural similarities with FGFs. However, despite these similarities, there are properties which set them apart from FGFs. FHFs lack the secretion signal sequence unlike other FGF members, except FGF1 and 2. Unlike FGFs, FHFs are not able to bind to FGF Receptors (FGFRs) and instead have been implicated in binding to Voltage-Gated Sodium Channels (VGSCs), neuronal MAP kinase scaffold protein and islet-brain-2 (IB2). The two amino acids Arg-52 and Val95 are conserved in all FHFs and mutation of these residues lead to its inability to bind with VGSC/IB2. However, it is not clear whether the loss of binding is due to destabilization of the protein on mutation or due to involvement of Arg52 and Val95 in conferring functionality to FHFs. Objective: In the present study, we have mutated these two conserved residues of FHF2 with its...

Combinatorial Chemistry & High Throughput Screening, 2014

Modulation of gamma-secretase cleavage of Amyloid Precursor Protein (APP) to control the level of... more Modulation of gamma-secretase cleavage of Amyloid Precursor Protein (APP) to control the level of Amyloid-beta (A-beta) peptide is one of the strategies to develop therapy for Alzheimer's disease. Presenilin is a subunit and the catalytic core of gamma-secretase. It has Asp 257 and Asp 385 residues, which are essential for catalytic activity and thus serve as the region of interest for screening of potential gamma-secretase inhibitors. In the present study, in silico screening of drug molecules has been performed in an attempt to identify effective inhibitors of presenilin. Ligand-based pharmacophore models generated with reported inhibitor molecules have been used as query for screening from DrugBank database. Inhibitory activity (IC50) of the screening hits is predicted using a QSAR model developed. The selected molecules have been subjected to docking study against Presenilin1 C-terminal fragment that houses Asp 385 in place of presenilin, as its structure is unavailable. Finally, 46 potential inhibitor molecules were selected based on scores of scoring function and interaction with Asp 385. The selected compounds have spatial arrangement of features essential for binding to presenilin, desired inhibitory activity against processing of APP to A-beta by gamma-secretase and selective interaction with specific amino acids in ligand-protein docked complexes.

Journal of Peptide Science, 2013

The transformation of polypeptide chains from their globular native structure to fibrillar aggreg... more The transformation of polypeptide chains from their globular native structure to fibrillar aggregates has been a matter of great concern because of the involvement of these aggregates in the onset of several degenerative diseases. These aggregates exhibit highly ordered cross β sheet structures and are known as 'amyloids'. Formation of amyloids in the body is associated with cytotoxicity due to direct interaction of the aggregated species with the cell membrane leading to cellular permeability or due to loss of functionality of the proteins involved in the amyloid formation. The preference of polypeptide chains to remain in their native conformation or to aggregate into amyloids is guided by several factors such as its conformation at specific condition, concentration, physicochemical properties of the amino acid sequence and so on. In the current review, we have reviewed the different factors that guide the transition of proteins from their natively folded state to the amyloidogenic state. Understanding the critical determinants of amyloidogenesis is vital towards deciphering the molecular mechanism of amyloidogenesis and for the development of effective therapeutics against amyloidosis.

BMB reports, 2008

Trypanothione reductase is an important target enzyme for structure-based drug design against Lei... more Trypanothione reductase is an important target enzyme for structure-based drug design against Leishmania. We used homology modeling to construct a three-dimensional structure of the trypanothione reductase (TR) of Leishmania infantum. The structure shows acceptable Ramachandran statistics and a remarkably different active site from glutathione reductase(GR). Thus, a specific inhibitor against TR can be designed without interfering with host (human) GR activity. [BMB reports 2008; 41(6): 444-447]

3 Biotech

Amyloidogenesis is the inherent ability of proteins to change their conformation from native stat... more Amyloidogenesis is the inherent ability of proteins to change their conformation from native state to cross β-sheet rich fibrillar structures called amyloids which result in a wide range of diseases like Parkinson's disease, Alzheimer's disease, Finnish familial amyloidosis, ATTR amyloidosis, British and Danish dementia, etc. COVID-19, on the other hand is seen to have many similarities in symptoms with other amyloidogenic diseases and the overlap of these morbidities and symptoms led to the proposition whether SARS-CoV-2 proteins are undergoing amyloidogenesis and whether it is resulting in or aggravating amyloidogenesis of any human host protein. Thus the SARS-CoV-2 proteins in infected cells, i.e., Spike (S) protein, Nucleocapsid (N) protein, and Envelope (E) protein were tested via different machinery and amyloidogenesis in them were proven. In this review, we will analyze the pathway of amyloid formation in S-protein, N-protein, E-protein along with the effect that SARS-CoV-2 is creating on various host proteins leading to the unexpected onset of many morbidities like COVID-induced Acute Respiratory Distress Syndrome (ARDS), Parkinsonism in young COVID patients, formation of fibrin microthrombi in heart, etc., and their future implications.

Journal of Molecular Structure

bioRxiv, 2022

Alzheimer’s Disease is a neurodegenerative disease for which no cure is available at present. The... more Alzheimer’s Disease is a neurodegenerative disease for which no cure is available at present. The presence of amyloid plaques in the extracellular space of neural cells is the key feature of this fatal disease. Amyloid-Beta (Aβ) is a 40-42 amino acid peptide and the main component of amyloid plaques. This peptide is produced by the proteolysis of Amyloid Precursor Protein by presenilin. Deposition of 42 residual Aβ peptides forms fibrils structure, leading to disruption of neuron synaptic transmission, inducing neural cell toxicity, ultimately leading to neuron death. To modulate the amyloidosis of Aβ peptides, various novel peptides have been investigated via molecular docking and molecular dynamic simulation studies. The sequence-based peptides were designed and investigated for their interaction with Aβ42 monomer and fibril using the molecular docking method, and their influence on the structural stability of target proteins was studied using molecular simulations. According to t...

Advances in Natural Sciences: Nanoscience and Nanotechnology, 2022

In this work, the core carbon nanoparticles (BM CNs) and polyethylene glycol 400 (PEG400)-capped ... more In this work, the core carbon nanoparticles (BM CNs) and polyethylene glycol 400 (PEG400)-capped BM CNs were synthesised from Butea monosperma flower extract via the facile direct heating method. They were investigated for their intriguing properties and in vitro antioxidation activity in comparison with Carica papaya seed (CPS) extract via DPPH assay. The CNs were characterised by DLS, XRD, HR-TEM, TGA, FT-IR, UV–vis spectral analysis and quantum yield measurement. The PEGylated CNs demonstrated decent quantum yield, favourable size, and turbostratic carbon phase apart from better stability and dispersion nature as compared to the uncapped entity. The mildly stable uncapped sample with zeta potential −17.9 mV featured its extensively aggregated form, unlike the capped sample with −23.0 mV zeta potential, which sheds light on its enhanced stability by PEG400. Antiradical capacities of the CNs in comparison with CPS extract demonstrated the PEG400-bound nanomaterial of its superior a...

Protein & Peptide Letters, 2022

: Amyloid fibrils are highly stable protein fibrillar aggregates believed to be involved in vario... more : Amyloid fibrils are highly stable protein fibrillar aggregates believed to be involved in various neurodegenerative diseases, which include Alzheimer’s disease, Parkinson’s disease, and prion diseases. Inhibiting the aggregation process is a potential strategy to prevent diseases caused by amyloid formation. In this regard, nanoparticles have emerged as promising candidates owing to their unique physical/chemical properties of small size, large surface area, biocompatibility, biodegradability, non-toxicity, and ease of functionalization. Human Serum Albumin (HSA) is a soluble multidomain monomeric protein that interacts with various ligands and hormones, aiding in their transport, distribution, metabolism in the circulatory system, and also plays a vital role in extracellular fluid volume stabilization. Under certain in vitro conditions, HSA has been reported to undergo conformational changes leading to fibril formation and hence acts as a suitable model for studying amyloidogenesis. In this review, we have explored the effects of various nanoparticles on HSA aggregation and their mechanism of action. The study will throw light on the mechanistic details of nanoparticle-mediated amyloid modulation, which will help in the development of effective therapeutics against amyloidosis.

Archives of Biochemistry and Biophysics, 2021

All proteins have the inherent ability to undergo transformation from their native structure to a... more All proteins have the inherent ability to undergo transformation from their native structure to a β sheet rich fibrillar structure, called amyloid when subjected to specific conditions. Proteins with a high propensity to form amyloid fibrils have been implicated in a variety of disorders like Alzheimer's disease, Parkinson's disease, Type II diabetes, Amyotrophic Lateral Sclerosis (ALS) and prion diseases. Among the various critical factors that modulate the process of amyloid formation, disulfide bonds have been identified as one of the key determinants of amyloid propensity in proteins. Studies have shown that intra-molecular disulfide bonds impart stability to the native structure of a protein and decrease the tendency for amyloid aggregation, whereas intermolecular disulfide bonds aid in the process of aggregation. In this review, we will analyze the varying effects of both intra as well as inter-molecular disulfide bonds have on the amyloid aggregation propensities of few proteins associated with amyloid disorders.

Current Proteomics, 2021

Background: Amyloids are a class of ordered protein aggregates which have been implicated in the ... more Background: Amyloids are a class of ordered protein aggregates which have been implicated in the onset of several degenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Type II diabetes, and so on. Despite extensive research, the exact mechanism and the driving factors for the amyloidogenesis process remain elusive. Identifying molecules which can effectively inhibit and/or disaggregate the fibrils may be one effective therapeutic strategy against amyloidosis. Objectives: In the current study, few hydroxy-benzoic phytochemicals were selected to study their effects on the formation as well as disaggregation of Hen Egg-White Lysozyme (HEWL) amyloids, namely gallic acid, syringic acid, vanillic acid, and iso-vanillic acid. Method: Amyloidogenesis was monitored using methods like the thioflavin T assay, Field Emission Scanning Electron Microscopy (FESEM), and dynamic light scattering (DLS) studies. Further protein conformational changes were monitored using methods lik...

Archives of Biochemistry and Biophysics, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Protein & Peptide Letters, 2019

Amyloids are highly ordered beta sheet rich stable protein aggregates, which have been found to p... more Amyloids are highly ordered beta sheet rich stable protein aggregates, which have been found to play a significant role in the onset of several degenerative diseases such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Type II diabetes mellitus and so on. Aggregation of proteins leading to amyloid fibril formation via intermediate(s), is thought to be a nucleated condensation polymerization process associated with many pathological conditions. There has been extensive research to identify inhibitors of these disease oriented aggregation processes. In recent times, quantum dots, with their unique physico-chemical properties have grabbed the attention of scientific community due to its applications in medical sciences. Quantum dots are nano-particles usually made of semiconductor materials which emit fluorescence upon radiation. The wavelength of fluorescence emission varies with changes in size of quantum dots. Several studies have reported significant inhibitory e...

Colloids and Surfaces B: Biointerfaces, 2019

Amyloid fibrils are the hallmarks of neurodegenerative diseases like Alzheimer's, Parkinson's and... more Amyloid fibrils are the hallmarks of neurodegenerative diseases like Alzheimer's, Parkinson's and other proteopathies. Inhibition of fibrillation is a potential strategy to check the progress of amyloid associated diseases and further allied deterioration. In this study, we have synthesized proline functionalized gold nanoparticles (Pro-AuNPs) and scrutinized its antifibrillation property towards Hen Egg White Lysozyme (HEWL) aggregation. Pro-AuNPs were characterized using various biophysical methods like ultraviolet-visible spectroscopy, fourier transform infra-red spectroscopy, zeta potential measurement, dynamic light scattering and transmission electron microscopy. The effect of Pro-AuNPs on HEWL fibrillation was analyzed employing thioflavin T (ThT) and 8-Anilino-1-naphthalenesulfonic acid (ANS) assays. The kinetics of HEWL exhibited a typical sigmoidal nature of protein aggregation and was fitted to Boltzmann model. HEWL in the presence of bare gold nanoparticles (bAuNPs) exhibited similar aggregation kinetics as HEWL alone. However, HEWL fibrillation substantially reduced upon co-incubation with proline and Pro-AuNPs, and two slightly different intermediate species were formed with these two systems as predicted by CD spectroscopy. TEM images also supported the above observation displaying different morphological states of HEWL aggregates in the presence of proline and Pro-AuNPs. Using computational methods, the nature of interaction of HEWL and proline was found to be hydrogen bonding and hydrophobic interaction in multiple amyloidogenic regions. These interactions inhibited the formation of prefibrils (β-sheet rich intermediates) and also found to disintegrate fibrils. Furthermore, HEWL-Pro-AuNPs system resulted HEWL adsorption through hydrophobic patches, which blocked the intermolecular βsheet formation. The present study successfully established Pro-AuNPs as a potential inhibitor of HEWL aggregation.

Biomedicines, 2017

Protein amyloids are characterized by aggregates that usually consist of fibres containing misfol... more Protein amyloids are characterized by aggregates that usually consist of fibres containing misfolded proteins and having a cross β-sheet conformation. These aggregates can eventually lead to several degenerative diseases like Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Huntington’s disease and Parkinson’s disease. The present study describes the effect of chemically synthesized polyvinylpyrrolidone (PVP)-conjugated gold nanoparticles (PVP-AuNps) on hen egg white lysozyme (HEWL) amyloids. The synthesized nanoparticles have been characterized using various biophysical techniques like Ultraviolet-Visible (UV-Vis) Spectroscopy, Transmission electron microscopy (TEM), X-ray diffraction (XRD) analysis, dynamic light scattering (DLS), zeta-potential measurement and Fourier transform infrared spectroscopy (FTIR). The aggregation studies showed that PVP acts as a partial inhibitor of HEWL amyloidogenesis. However, when conjugated to gold nanoparticle surface, it leads to comple...

The Protein Journal, 2017

Current Trends in Biotechnology and …, 2008

Trypanothione synthetase(TryS) is an important enzyme for survival of Leishmania; thus an importa... more Trypanothione synthetase(TryS) is an important enzyme for survival of Leishmania; thus an important target for structure based drug design against leishmaniasis. We have constructed three-dimensional structure of the TryS of Leishmania infantum by homology modeling with acceptable ...

Biopolymer-Based Formulations, 2020

Protein & Peptide Letters

Background: Fibroblast growth Factor Homologous Factors (FHFs) belong to a subclass of Fibroblast... more Background: Fibroblast growth Factor Homologous Factors (FHFs) belong to a subclass of Fibroblast Growth Factor (FGF) family owing to their high sequence and structural similarities with FGFs. However, despite these similarities, there are properties which set them apart from FGFs. FHFs lack the secretion signal sequence unlike other FGF members, except FGF1 and 2. Unlike FGFs, FHFs are not able to bind to FGF Receptors (FGFRs) and instead have been implicated in binding to Voltage-Gated Sodium Channels (VGSCs), neuronal MAP kinase scaffold protein and islet-brain-2 (IB2). The two amino acids Arg-52 and Val95 are conserved in all FHFs and mutation of these residues lead to its inability to bind with VGSC/IB2. However, it is not clear whether the loss of binding is due to destabilization of the protein on mutation or due to involvement of Arg52 and Val95 in conferring functionality to FHFs. Objective: In the present study, we have mutated these two conserved residues of FHF2 with its...

Combinatorial Chemistry & High Throughput Screening, 2014

Modulation of gamma-secretase cleavage of Amyloid Precursor Protein (APP) to control the level of... more Modulation of gamma-secretase cleavage of Amyloid Precursor Protein (APP) to control the level of Amyloid-beta (A-beta) peptide is one of the strategies to develop therapy for Alzheimer's disease. Presenilin is a subunit and the catalytic core of gamma-secretase. It has Asp 257 and Asp 385 residues, which are essential for catalytic activity and thus serve as the region of interest for screening of potential gamma-secretase inhibitors. In the present study, in silico screening of drug molecules has been performed in an attempt to identify effective inhibitors of presenilin. Ligand-based pharmacophore models generated with reported inhibitor molecules have been used as query for screening from DrugBank database. Inhibitory activity (IC50) of the screening hits is predicted using a QSAR model developed. The selected molecules have been subjected to docking study against Presenilin1 C-terminal fragment that houses Asp 385 in place of presenilin, as its structure is unavailable. Finally, 46 potential inhibitor molecules were selected based on scores of scoring function and interaction with Asp 385. The selected compounds have spatial arrangement of features essential for binding to presenilin, desired inhibitory activity against processing of APP to A-beta by gamma-secretase and selective interaction with specific amino acids in ligand-protein docked complexes.

Journal of Peptide Science, 2013

The transformation of polypeptide chains from their globular native structure to fibrillar aggreg... more The transformation of polypeptide chains from their globular native structure to fibrillar aggregates has been a matter of great concern because of the involvement of these aggregates in the onset of several degenerative diseases. These aggregates exhibit highly ordered cross β sheet structures and are known as 'amyloids'. Formation of amyloids in the body is associated with cytotoxicity due to direct interaction of the aggregated species with the cell membrane leading to cellular permeability or due to loss of functionality of the proteins involved in the amyloid formation. The preference of polypeptide chains to remain in their native conformation or to aggregate into amyloids is guided by several factors such as its conformation at specific condition, concentration, physicochemical properties of the amino acid sequence and so on. In the current review, we have reviewed the different factors that guide the transition of proteins from their natively folded state to the amyloidogenic state. Understanding the critical determinants of amyloidogenesis is vital towards deciphering the molecular mechanism of amyloidogenesis and for the development of effective therapeutics against amyloidosis.

BMB reports, 2008

Trypanothione reductase is an important target enzyme for structure-based drug design against Lei... more Trypanothione reductase is an important target enzyme for structure-based drug design against Leishmania. We used homology modeling to construct a three-dimensional structure of the trypanothione reductase (TR) of Leishmania infantum. The structure shows acceptable Ramachandran statistics and a remarkably different active site from glutathione reductase(GR). Thus, a specific inhibitor against TR can be designed without interfering with host (human) GR activity. [BMB reports 2008; 41(6): 444-447]