Indian journal of biochemistry & biophysics最新文献

{"title":"Protein Carbamylation in Neurodegeneration and other age-related disorders","authors":"","doi":"10.56042/ijbb.v60i9.4103","DOIUrl":"https://doi.org/10.56042/ijbb.v60i9.4103","url":null,"abstract":"Ageing is a complex process that is greatly influenced by environmental and genetic factors. Ageing at the cellular and molecular level is characterized by the accumulation of post-translationally modified proteins that are derogative to cells, termed Degenerative protein modification (DPM). A particular class of DPM, occurring under the impact of urea, termed brain ureido degenerative post-translational modifications (uDPM) has also been implicated in the molecular pathogenesis of Alzheimer's disease and related neurodegenerative disorders. These modifications can disrupt normal protein functions by altering their conformation, enzymatic activities, receptor recognitions, and physiological capabilities. Carbamylation is an age-related uDPM that results from the non-enzymatic modification of amino groups of ε-amino groups on lysine in proteins. The significance of carbamylation in some age-related disorders such as cataracts, rheumatoid arthritis,and cardiovascular diseases is well documented.However, the role of carbamylation in the pathogenesis of various neurodegenerative disorders, which are also age-dependent, has not been explored much. The aim of the current article is a retrospection of carbamylation, its effect on proteins, and its implications in ageing and neurodegenerative diseases. Carbamylation is one such age-related uDPM, which results from the non-enzymatic modification of amino groups of ε-amino groups on lysines or N-terminal amino groups present in proteins or peptides by isocyanate. The significance of carbamylation in some age-related disorders such as cataracts, rheumatoid arthritis, and cardiovascular diseases is well documented. However, the role of carbamylation in the pathogenesis of various neurodegenerative disorders, which are also age-dependent, has not been explored much. This mini-review will focus on the relationship between carbamylation and neurodegenerative disorders and provide an overview of the process of carbamylation, its contribution towards molecular ageing of protein, and the involvement of carbamylation in neurodegeneration and related diseases associated with ageing.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135494912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of neuroprotective effects of medium chain fatty acids and their derivatives on mutant huntingtin aggregates, oxidative stress and ATP levels in HD150Q cell line model of Huntington’s disease","authors":"","doi":"10.56042/ijbb.v60i9.4047","DOIUrl":"https://doi.org/10.56042/ijbb.v60i9.4047","url":null,"abstract":"Huntington's disease (HD) is a rare autosomal dominant genetic disorder resulting from expansion of polymorphic CAG repeats in the exon 1 of huntingtin gene that translates into elongated polyglutamine (ployQ) tract in huntingtin protein (HTT).PolyQ expansion alters HTT structure resulting in abnormal protein-protein interactions, aggregation, mitochondrial dysfunction, oxidative and endoplasmic reticulum stress, inflammation and altered gene expression leading to neuronal cell death.HD symptoms involves chorea, dementia, behavioural and psychological problems and currently there is no cure highlighting the need for novel therapeutic interventions. Several fatty acids have been reported to have protective effects in neurological disorders including Alzheimer’s disease, Parkinson’s disease and epilepsy. However, their effects in HD is largely unexplored. Neurodegenerative diseases share several common pathways and thus it is likely that a combination of selected fatty acids show neuroprotective effects in HD. This study utilized a cell line model of HD expressing inducible mutant huntingtin fragment with 150 polyQ repeats (HD150Q) to investigate neuroprotective effects of two medium chain fatty acids and one triglyceride. Significant reduction in mutant HTT aggregates and mitochondrial oxidative stress and restoration of ATP levels was observed upon treatment with Decanoic acid, 2-butyloctanoic acid, and Glyceryl triacetate. Encouraging results in the cell line model opens avenues for investigating the underlying molecular mechanisms and validation in the animal models.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135495134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant and Anticancer Activity of Rhynchosia rufescens (Willd.) DC.","authors":"","doi":"10.56042/ijbb.v60i11.717","DOIUrl":"https://doi.org/10.56042/ijbb.v60i11.717","url":null,"abstract":"The present study deals with the chemical composition, antioxidant, antimicrobial and anticancer efficacy of Rhynchosia rufescens (RR) leaf methanol (RRME), ethyl acetate (RREAE) and petroleum ether (RRPE) extracts. Preliminary phytochemical results revealed that alkaloids, coumarins, flavonoids, volatile oils, fatty acids, and phenols were present in the test extracts. Gas chromatographic analysis of RRPE revealed the identification of 25 volatile compounds. The oil contains monoterpenes (9.6%) and fatty acids (6.12%). The major components of the oil are beta- copaene (32.06%), cyclofenchene (16.53%), beta- pinene (5.69%), 3-carene (3.48%) and sabinene (3.22%). Quantitative estimation of total phenols (TPC) and flavonoids (TFC) indicated that TPC ranged from 8.99 ±1.00 to 60.00±1.15 mg GAE/g dry weight and TFC was between 4.98±0.08 to 20.4±0.50 mg QE/ g dry weight respectively. Methanol extract showed the highest phosphomolybdenum dependent antioxidant capacity, while ethyl acetate extracts strongly inhibited DPPH and hydroxyl radicals. Anticancer study results revealed that ethyl acetate extract enhanced caspase-3 mediated DNA fragmentation in HCT – 116 cell lines than standard cisplatin. In conclusion, R. rufescens extracts showed potent antioxidant, antibacterial activity and potential anticancer activity in HCT-116 cell lines. The observations of this study indicated that R. rufescens extracts are a rich source of natural antioxidants and anticancer components.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135610482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Newly-discovered behaviour in the bacterial histone-like protein, HU","authors":"","doi":"10.56042/ijbb.v60i9.4572","DOIUrl":"https://doi.org/10.56042/ijbb.v60i9.4572","url":null,"abstract":"This paper summarizes the contents of a talk delivered at the MS University of Baroda (Vadodara, Gujarat) on 3rd March, 2023, at a conference held to celebrate proteins in commemoration of the birth centenary of Prof. G. N. Ramachandran. Here, we review several recent discoveries and applications from our group that relate to HU, a DNA-binding nucleoid-associated protein found in bacteria: (1) HU uses its DNA-binding sites to bind to lipopolysaccharide (LPS) upon bacterial cell surfaces, in the extracellular milieu in biofilms, thus working as a glue to attach bacteria to extracellular DNA; (2) HU and DNA perform mutual macromolecular crowding, as well as mutual charge neutralization, to together undergo condensation into nucleoids that appear to maintain DNA in a compacted state in bacterial genomes through liquid-liquid phase separation (LLPS); (3) HU appears to have evolved to avoid use of the amino acid residue, tryptophan, to avoid damage to bacterial genomic DNA by a combination of sunlight and photosensitized oxidation by tryptophan photodecomposition products; (4) HU’s N-terminal (positive) charge destabilizes hydrophobic inter-subunit interactions between beta strands in HU dimers and promotes subunit exchange between HU-A and HU-B (the two isoforms of HU in gut bacteria), thus hindering the facile dissociation of subunits if an N-terminal 6xHis affinity tag is present; (5) HU-A and HU-B can be genetically fused to generate a simulacrum of an HU heterodimer; (6) HU’s DNA-binding regions from two bacterial homologs (one mesophilic and the other thermophilic) can be isolated and genetically fused to generate a novel thermostable DNA-binding protein; (7) HU’s ability to titrate onto the bacterium’s nucleoid can be exploited to deploy fluorescent protein-labelled HU in cells to test for leaky expression from bacterial promoters, using fluorescence microscopy.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135495133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyphenol MHQP as an allosteric inhibitor of Kinesin-5: Cease the molecular catwalk of “Drunken Sailor”","authors":"","doi":"10.56042/ijbb.v60i9.4056","DOIUrl":"https://doi.org/10.56042/ijbb.v60i9.4056","url":null,"abstract":"Human Kinesin-5 (KIF-11/Eg5), a major anticancer drug target, is a plus end-directed motor protein that is involved in spindle dynamics and principally involved in mitosis. In the present study, a computer-aided rational drug discovery approach has been applied to search for potential allosteric inhibitors against Eg5. Accordingly, virtual screening of naturally occurring secondary metabolites and their commercially available synthetic derivatives indicates 2-(9b- methyl-2,3,3a,4,5,9b-hexahydrofuro [3,2 c] quinolin-4-yl) phenol (MHQP), a hexahydrofuro [3,2-c] quinolone derivative as a potential therapeutic lead molecule against Eg5. The present study provides a structural glimpse of MHQP binding at the monastrol binding site of Eg5 with a vivid description of its plausible mode of Eg5 inhibition. Moreover, the in silico data also supports the superiority of MHQP over the well-characterized Eg5 inhibitor Arry-520 in terms of augmented binding affinity as well as to cope with Arry-520 resistant mutants of Eg5. Structure-guided mechanistic details of MHQP-induced inhibition of Eg5 and its predicted pharmacodynamics properties have been presented herein.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135494896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative study of anti-diabetic effects of insulin, epigenin and Salvia mirzayanii extract in streptozotocin-induced diabetic male rats","authors":"","doi":"10.56042/ijbb.v60i10.1228","DOIUrl":"https://doi.org/10.56042/ijbb.v60i10.1228","url":null,"abstract":"The use of hypoglycemic medications for diabetes has several limitations, such as adverse reactions and high rates of secondary failure. These adverse effects have forced patients with diabetes to use herbal medicines that have a similar degree of potency without side effects. So, there has been a growing interest in hypoglycemic agents from natural products, in particular, those derived from plant materials. In other words, searching for better agents from herbs or natural products to treat diabetes is duly needed. The purpose of this study was to compare the anti-diabetic effects of Salvia mirzayanii extract with insulin and epigenin in diabetic male rats. The plant material was initially extracted and administered orally to the animals. After treatment of rats with insulin, epigenin or aqueous extract of S. mirzayanii, oral glucose tolerance test (OGTT), fasting blood glucose and animal weight changes were examined. To analyze the molecular function of insulin, epigeninand S. mirzayanii, expression of glucose transporter-4 (GLUT4), phosphoenol pyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase) genes in healthy and streptozotocin (STZ)-diabetic male rats were studied as well. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed for all groups and the data were normalized using the formula 2-ΔΔCt.Statistical analysis was performed by one-way analysis of variance. In fasting blood glucose and OGTT, there was no significant difference between the normal control group and the diabetic groups treated with insulin, epigenin and S. mirzayanii. But there was a significant difference with the uncontrolled diabetic group (P < 0.05). Meanwhile, the uncontrolled diabetic group gained less weight compared to the other groups. RT-qPCR of beta-actin, GLUT4, G6Pase and PEPCK genes yielded products with lengths of 228, 140, 79 and 151 bp, respectively. In gene expression studies, there was a significant difference between the mRNA levels of GLUT4, G6Pase and PEPCK in control groups and the groups treated with insulin, epigenin and S. mirzayanii. The greatest effect on increasing the mRNA expression of GLUT4 was related to insulin, epigenin and S. mirzayanii, respectively. The greatest effect in reducing the mRNA expression of PEPCK was related to insulin, epigenin and S. mirzayanii, respectively. The greatest effect in reducing the mRNA expression of G6Pase was also related to insulin, but the effect of epigenin and S. mirzayaniiwas almost the same. Overall, obtained results show that S. mirzayanii can be utilized as a herbal medication with insulin and epigenin mimetic-activity.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135799266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and development of mutant EGFR inhibitors from a structural perspective","authors":"","doi":"10.56042/ijbb.v60i9.3967","DOIUrl":"https://doi.org/10.56042/ijbb.v60i9.3967","url":null,"abstract":"Molecules targeting non-small cell lung cancer driven by activating mutations within the epidermal growth factor receptor (EGFR) are highly effective but acquired drug resistance remains a persistent challenge. Insights from structural pharmacology and medicinal chemistry have aided in detailed understanding of the structural basis for how these inhibitors gain their mutant EGFR selective inhibitory activity and inform state-of-the-art drug design. The novel third-generation EGFR tyrosine kinase inhibitor (TKI) YH25448 (lazertinib) binds to EGFR with T790M-targeting van der Waals interactions and intramolecular hydrogen bonds consistent with improved medicinal chemistry properties compared to AZD9291 (osimertinib). Additionally, fourth-generation TKIs targeting the drug resistant C797S mutation comprise diverse structural features, but all share hydrogen bonding capabilities with the K745 catalytic residue consistent with stronger binding. Finally, inspired by the synergy seen between ATP and allosteric inhibitors, bivalent EGFR inhibitors have emerged showing potential for compounds with structurally diverse binding modes. Insights from these combined structural and functional studies offer key insights into the development of next-generation EGFR TKIs and inspire further exploration of similar binding features more broadly in protein kinases.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135494907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, DFT and Molecular docking study of novel bis 1,2,3-triazole derivatives of 2-hydroxyquinoline-4-carboxylate as antimicrobial agents","authors":"","doi":"10.56042/ijbb.v60i9.3877","DOIUrl":"https://doi.org/10.56042/ijbb.v60i9.3877","url":null,"abstract":"A series of novel bis 1,2,3-triazole derivatives of 2-Hydroxyquinoline-4-carboxylate, exhibiting diverse molecular structures were synthesized through a click reaction, incorporating a combination of 1,2,3-triazole moieties and quinoline nucleus. In vitro biological studies were conducted to evaluate their antitubercular, antibacterial and antifungal activities. To explore the behavioural and selective properties of the synthesized molecules, experimental analysis was complemented with computational methods. Density functional theory (DFT) calculations were performed to examine electronic and structural parameters, while molecular docking studies were conducted to gain insight into the structural basis of activity against MTB InhA inhibitors, DNA gyrase B protein of Staphylococcus aureus (a Gram positive bacterium) and DHFR of Candida albicans fungi. Theoretical calculations were consistent with the observed antibacterial and antifungal activity in the experimental data.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135496272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solution structures and thermodynamics of cis-trans X-Pro conformers of a novel single disulfide conopeptide","authors":"","doi":"10.56042/ijbb.v60i9.4061","DOIUrl":"https://doi.org/10.56042/ijbb.v60i9.4061","url":null,"abstract":"The conopeptide Mo1853 (MW = 1853 Da) consists of 17 residues and a single disulfide bond. Structural studies using homonuclear solution NMR methods (2D 1H,1H DQF-COSY, TOCSY, NOESY and ROESY spectra) revealed that Mo1853 exists as two equally populated cis and trans X–Pro peptide bond conformers which are in slow exchange regime, compared to the chemical shift time scale. Temperature dependence of chemical shifts was measured and using coalescence temperature of two amide protons, the rate of exchange and the free energy of activation for the conformational exchange were determined to be 59 Hz and ≈ 67.2 kJ mol−1, respectively, at 318 K. Additional evidence for this conformational equilibrium was also observed as exchange correlation peaks in the 2D-NOESY and ROESY spectra. Tertiary structures of both the cis (PDB ID 8K3N) and trans (PDB ID 8K3M) conformers were determined using distance restraints, backbone dihedral angle restraints, the disulfide bond restraint and the cis or trans conformation of the X–Pro peptide bond. The trans conformer of Mo1853 is stabilized by hydrogen bonds while the cis conformer seems to be stabilized predominantly by hydrophobic interactions. This was further corroborated by the fact that at lower temperatures, the hydrophobic interactions became weaker reducing the population of the cis conformer with respect to that of the trans conformer. The cis and trans X–Pro peptide bond conformational exchange could be another means to enhance the structural variability of the conopeptides and could have significance in the synergistic functional response caused by the cone snail venom peptides.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135495137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation, purification and characterization of a protease from the seeds of Artocarpus heterophyllus","authors":"","doi":"10.56042/ijbb.v60i9.4053","DOIUrl":"https://doi.org/10.56042/ijbb.v60i9.4053","url":null,"abstract":"Proteases are being widely used in various industries like detergent, leather, food and pharmaceuticals.Protease was purified to homogeneity from the seeds of Artocarpus heterophyllus. The enzyme was found to be a tetramer having molecular mass of 74 kDa. Gelatin zymography showed a clear band of proteolysis. The enzyme isolated and purified was a serine protease, as indicated by its inhibition with PMSF. The enzyme was stable at broad pH and temperature ranges with pH and temperature optima at 8.5 and 50°C, respectively. The presence of some divalent ions enhanced the activity. With the addition of calcium, change in absorption and emission spectra was observed in spectrofluorometric analysis. The Km and Vmax for the enzyme was found to be 0.229 µM and 0.014 µM min-1, respectively, using BAPNA as a substrate. The enzyme consisted 4.44% alpha helix and 44.17% beta sheets when measured by CD spectra. Dynamic light scattering of the protease for particle size distribution revealed the mono-dispersity of the sample. Easy purification and paramount stability of protease makes it a good candidate for industrial and pharmaceutical applications.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135495141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}