The Protein Journal最新文献

{"title":"Therapeutic Potential of FTO Demethylase in Metabolism and Disease Pathways","authors":"Chaitanya Sree Somala,&nbsp;Selvaraj Sathyapriya,&nbsp;Nagaraj Bharathkumar,&nbsp;Thirunavukarasou Anand,&nbsp;Damal Chandrasekar Mathangi,&nbsp;Konda Mani Saravanan","doi":"10.1007/s10930-025-10250-3","DOIUrl":"10.1007/s10930-025-10250-3","url":null,"abstract":"<div><p>The crucial involvement of the Fat Mass and Obesity-associated (FTO) protein in both metabolic and non-metabolic diseases has been documented since its discovery. This enzyme, known as FTO, is a demethylase that belongs to the 2-oxoglutarate-dependent nucleic acid demethylases. Its primary function is to target N6-methyladenosine (m⁶A) in RNA, which is crucial in regulating RNA stability, processing, and expression. This review facilitates understanding the FTO gene variations linked to Body Mass Index (BMI) and obesity, resulting in increased vulnerability to type 2 diabetes. While prior reviews have already discussed the link between FTO and BMI and its impact on type 2 diabetes, the current review additionally examines the emerging evidence suggesting a direct influence of the FTO gene on metabolism. Additionally, the paper discusses the alternative role of FTO and emphasizes the endophenotypes in neurological circuits and the demethylase function of FTO in neurodegenerative disorders. The review further examines the impact of FTO on several physiological systems and emphasizes the need to study FTO as a potential multitarget for future research and therapies.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"44 1","pages":"21 - 34"},"PeriodicalIF":1.9,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375104","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":"Impression of Insect’s Proteolytic Enzyme Cocoonase and Its Application: A Comprehensive Review","authors":"Aruna Rani,&nbsp;Dev Mani Pandey,&nbsp;Jay Prakash Pandey","doi":"10.1007/s10930-024-10246-5","DOIUrl":"10.1007/s10930-024-10246-5","url":null,"abstract":"<div><p>Cocoonase is a naturally secreted protease responsible for facilitating moth emergence from inside of cocoon. This protease is considered as of prime importance for all the cocooning lepidopteron. It specifically degrades sericin, the glue protein of the cocoon without damaging the fibroin and makes an escape hatch for adult emergence. Owing to this property cocoonase was characterized and explored for its prospective utilization in eco-friendly enzyme-based silk degumming. However, the applicability of cocoonase has not been explored much other than in silk degumming. Moreover, being a serine protease, and because of its similarity to trypsin, there is, tremendous potential for this enzyme to have biomedical applications, as well as numerous other uses that need to be investigated. This review article presents the comprehensive physicochemical properties of the cocoonase and its possible scope of applications in the near future.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"44 1","pages":"48 - 61"},"PeriodicalIF":1.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191200","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":"Ferguson Plot Analysis of Chaperone ClpB from Moderate Halophile","authors":"Teruo Akuta,&nbsp;Yui Tomioka,&nbsp;Tomoto Ura,&nbsp;Masataka Nakagawa,&nbsp;Tsutomu Arakawa","doi":"10.1007/s10930-024-10245-6","DOIUrl":"10.1007/s10930-024-10245-6","url":null,"abstract":"<div><p>The Ferguson plot is a simple method for determining the molecular weight of native proteins and their complexes. In this study, we tested the validity of the Ferguson plot based on agarose native gel electrophoresis using multimeric chaperone protein, ClpB, derived from a moderate halophile that forms a native hexamer. The Ferguson plot showed a single band with a molecular weight of 1,500 kDa, approximately twice the size of the native hexamer. This result is consistent with the structure of other chaperons that form a double ring assembly comprising two hexameric units, i.e., a dodecamer. Supporting this, dynamic light scattering experiment showed two peaks, which likely correspond to the hexamer and dodecamer structures.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"44 1","pages":"79 - 87"},"PeriodicalIF":1.9,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934152","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":"The Root-Tuber Trypsin Inhibitor of Winged Bean and Its Anti-cancerous Activity Against Osteosarcoma Cell-Line","authors":"Rayees Ahmad Lone,&nbsp;Bhupendra Kumar,&nbsp;Mohd. Kashif,&nbsp;Shafquat Fakhrah,&nbsp;Tofan Kumar Rout,&nbsp;Sahabjada Siddiqui,&nbsp;Rojalin Pattanayak,&nbsp;Pradhyumna Kumar Singh,&nbsp;Chandra Sekhar Mohanty","doi":"10.1007/s10930-024-10244-7","DOIUrl":"10.1007/s10930-024-10244-7","url":null,"abstract":"<div><p>Trypsin inhibitor from the root-tuber of underutilized legume Winged bean (<i>Psophocarpus tetragonolobus</i> (L.) DC.) (WbT-TI) was purified using ion exchange chromatography followed by size-exclusion chromatography. The purified WbT-TI showed a molecular mass of 20,609 Da and an isoelectric point of 5.10. Ultraviolet circular dichroism (UV-CD) and intrinsic fluorescence reported, that WbT-TI interacts with trypsin. Domain-wise analysis of WbT-TI revealed it to belong to the Kunitz-type soybean trypsin inhibitor (STI) family with a specific β-trefoil fold. The sequence of WbT-TI showed 44% sequence coverage to acidic trypsin inhibitor from the seed of the same plant. Protein interaction similarity analysis (PIPSA) evaluated the electrostatic properties of WbT-TI and provided information about the interacting partners of trypsin inhibitors. The purified protein was quantified and tested for in vitro anticancer activity using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay against the human osteosarcoma (MG-63) cell line. At 5 µg/ml of WbT-TI, the highest inhibition was seen. These studies may lead to the development of winged bean protease inhibitor-based preventive and therapeutic strategies for different kinds of cancers.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"44 1","pages":"88 - 101"},"PeriodicalIF":1.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866946","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":"Infrared Spectral Patterns of Thyroglobulin Bearing Thyroiditogenic Epitopes","authors":"Igor Cherepanov,&nbsp;Alexandr Sidorov,&nbsp;Liubov Beduleva,&nbsp;Alexey Terentiev,&nbsp;Daria Menshikova,&nbsp;Tatyana Khramova,&nbsp;Igor Menshikov,&nbsp;Pavel Ivanov","doi":"10.1007/s10930-024-10243-8","DOIUrl":"10.1007/s10930-024-10243-8","url":null,"abstract":"<div><p>Thyroglobulin is a major autoantigen to which autoimmune response, destroying the thyroid gland in Hashimoto’s thyroiditis, is directed. To detect a pathological autoimmune response to thyroglobulin, as well as the successful induction of experimental autoimmune thyroiditis, thyroglobulin carrying thyroiditogenic epitopes is necessary. It is not known which features of thyroglobulin structure determine the presence of thyroiditogenic epitopes and can serve as markers of their presence. We compared structure of thyroglobulin bearing thyroiditogenic epitopes (freshly isolated thyroglobulin) and thyroglobulin which had lost thyroiditogenic epitopes (lyophilized thyroglobulin). Fourier-transform infrared (FTIR) spectroscopy was used to elucidate the structure of thyroglobulin. The markers indicating the presence of thyroiditogenic epitopes on thyroglobulin are the vibrations of diiodotyrosine, monoiodotyrosine/diiodotyrosine relation in the range of 0.24–0.43 (95% confidence interval) and relatively high (&gt; 32%) α-helix content. The loss of thyroiditogenic epitopes on thyroglobulin is associated with a weakening or complete disappearance of diiodotyrosine oscillations and a decrease in the proportion of α-helices in secondary structure. Thyroglobulin extracted with phenylmethylsulfonyl fluoride (PMSF) added is characterized by the same relatively high monoiodotyrosine/diiodotyrosine relation and low proportion of alpha helices as thyroglobulin without thyroiditogenic epitopes. Therefore, serine protease inhibitor PMSF is not suitable for extraction of native thyroglobulin bearing thyroiditogenic epitopes. FTIR spectroscopy can be used to detect thyroiditogenic epitopes on thyroglobulin.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"44 1","pages":"68 - 78"},"PeriodicalIF":1.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780947","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":"Wasp Venom: Future Breakthrough in Production of Antimicrobial Peptides","authors":"Bikramjit Bhattacharya,&nbsp;Shreshtha Bhattacharya,&nbsp;Srinjana Khatun,&nbsp;Namitha A. Bhaktham,&nbsp;M. Maneesha,&nbsp;C. Subathra Devi","doi":"10.1007/s10930-024-10242-9","DOIUrl":"10.1007/s10930-024-10242-9","url":null,"abstract":"<p>The emergence of multi-drug-resistant pathogens and the decrease in the discovery of newer antibiotics have led to a quest for novel alternatives. Recently, wasp venom has spiked interest due to the presence of various active compounds, showcasing a diverse range of therapeutic effects. Wasps are creatures of the Hymenoptera order, and their venom chemically comprises antimicrobial peptides such as Anoplin, Mastoparan, Polybia-CP, Polydim-I, and Polybia MP1 that play a significant role in the biological effects of the venom. AMPs belong to the family of cationic peptides with α-helical structure, which exhibits a diversity of structural motifs and are crucial for innate immunity and defence in these creatures. These peptides demonstrate not only antimicrobial properties but also a wide range of other biological activities like anti-biofilm and anti-inflammatory, linked to their varying capacity to interact with biological membranes. Although wasp venom has the potential to be a cutting-edge natural source for the creation of new drugs, its usage is still restricted due to its availability and the lack of sophisticated methods for synthesizing its therapeutic components. Therefore, this review article provides insights about the therapeutic use of the wasp venom peptides against the antimicrobial-resistant pathogens, as well as its constraints and opportunities for future pharmacological development.</p>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"44 1","pages":"35 - 47"},"PeriodicalIF":1.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781219","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":"Exploring Acoustic Detection of α-Synuclein Fibrils","authors":"M. Brun-Cosme-Bruny,&nbsp;L. Gerfault,&nbsp;V. Mourier,&nbsp;N. Torres,&nbsp;P. Bleuet","doi":"10.1007/s10930-024-10241-w","DOIUrl":"10.1007/s10930-024-10241-w","url":null,"abstract":"<div><p>Over the past decades, the incidence of Parkinson’s disease (PD) cases has doubled in industrialized countries. While patients over 70 years old still represent more than half of the cases, the disease is increasingly affecting younger individuals. Environmental factors have been implicated, such as the effects of certain pesticides or chemicals on neurons, such as rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Researchers have also demonstrated the influence of genetic mutations in younger patients. A-synuclein is a protein encoded by the SNCA gene, known to undergo various mutations in hereditary cases of PD. These mutations alter the composition and spatial arrangements of α-synuclein. The proteins, originally of linear shape, aggregate during the progression of PD, forming fibrillary structures that propagate through brain tissues. Among the physical therapies investigated for treating α-synuclein aggregation, ultrasonic waves, capable of altering protein and cell behaviors, have recently been used to disrupt α-synuclein fibrils within tissues in cellular and animal models, with the hope of developing treatments based on ultrasound properties. However, detecting fibrils typically requires invasive and non-biocompatible chemical compounds or cumbersome machinery. In this study, our acoustic experimental setup allowed us to investigate the response of α-synuclein to ultrasound perturbations. By capturing the transmitted wave across proteins over a frequency range 10 kHz to 10 MHz, no ultrasound signature indicating the presence of proteins was observed.</p><p><b>Significance Statement</b>: The results report there is no ultrasound signature of the presence of α-synuclein fibrils, from 10 kHz to 10 MHz.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"44 1","pages":"62 - 67"},"PeriodicalIF":1.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10930-024-10241-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody Aggregation: A Problem Within the Biopharmaceutical Industry and Its Role in AL Amyloidosis Disease","authors":"Kate Sheehan,&nbsp;Hyesoo Jeon,&nbsp;Sinéad C. Corr,&nbsp;Jerrard M. Hayes,&nbsp;K. H. Mok","doi":"10.1007/s10930-024-10237-6","DOIUrl":"10.1007/s10930-024-10237-6","url":null,"abstract":"<div><p>Due to the large size and rapid growth of the global therapeutic antibody market, there is major interest in understanding the aggregation of protein products as it can compromise efficacy, concentration, and safety. Various production and storage conditions have been identified as capable of inducing aggregation of polyclonal and monoclonal antibody (mAb) therapies such as low pH, freezing, light exposure, lyophilisation and increased ionic strength. The addition of stabilising excipients to these therapeutics helps to combat the formation of aggregates with future aggregation inhibition mechanisms involving the introduction of point mutations and glycoengineering within aggregation prone regions (APRs). Antibody aggregation also plays an integral role in the pathogenesis of a condition known as amyloid light chain (AL) amyloidosis which is characterised by the production of improperly folded and amyloidogenic immunoglobulin light chains (LCs). Current diagnostic tools rely heavily on histological staining with their future moving towards amyloid component identification and proteomic analysis. For many years, treatment options designed for multiple myeloma (MM) have been applied to AL amyloidosis patients by depleting plasma cell numbers. More recently, treatment strategies more specific to this condition have been developed with many designed to recognize amyloid fibrils and trigger their degradation without causing systemic plasma cell cytotoxicity. Amyloid fibrils in AL disease and aggregates in antibody therapeutics are both formed through the oligomerisation of misfolded / modified proteins attempting to reach a thermodynamically stable, free energy minimum that is lower than the respective monomers themselves. Although the final morphologies are different, by understanding the principles underlying such aggregation, we expect to find common insights that may contribute to the development of new and effective methods of antibody aggregation and/or amyloidosis management. We envision that this area of research will continue to be very relevant in both industry and clinical settings.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"44 1","pages":"1 - 20"},"PeriodicalIF":1.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635640","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":"DAAO Mutant Sites among Different Mice Strains and Their Effects on Enzyme Activity","authors":"Zhou Yu-Cong,&nbsp;Fu Sheng-Ling,&nbsp;Liu Hao","doi":"10.1007/s10930-024-10235-8","DOIUrl":"10.1007/s10930-024-10235-8","url":null,"abstract":"<div><p>Previous studies reported that _D-amino acid oxidase (DAAO) activity was closely associated with neuropathic pain, cognitive characteristics of schizophrenia and so on. To determine DAAO mutant sites in different strains of mice and their effects on enzyme activity, we successfully constructed a prokaryotic expression system for heterologous expression of DAAO in vitro. There were total five nucleotide mutations distributed in exons 2, 8, 9, 10 of C57 mice. Three mutations located on exons 8 and 9 were synonymous mutations and had no variation on the encoded amino acid. The remaining two mutations in exons 2 (V64A) and 10 (R295H) were non-synonymous mutations, which might affect enzymatic activity and protein structure of mDAAO. Based on the determination of the kinetic constants and IC₅₀ of mDAAO mutants in vitro, the differences in amino acid levels at these two sites (V64A, R295H) increased the affinity of C57 DAAO with substrate and enhanced its catalytic efficiency. Besides, the IC₅₀ value of C57 DAAO was less than that of Balb/c and other DAAO mutants (SUN: reducted by about 11.9%; CBIO: reducted by about 26.5%), which meant that the affinity of C57 DAAO with CBIO was higher.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"44 1","pages":"102 - 112"},"PeriodicalIF":1.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565291","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":"Unraveling the interaction between a glycolytic regulator protein EhPpdk and an anaphase promoting complex protein EhApc10: yeast two hybrid screening, in vitro binding assays and molecular simulation study","authors":"Suchetana Pal,&nbsp;Pinaki Biswas,&nbsp;Raktim Ghosh,&nbsp;Somasri Dam","doi":"10.1007/s10930-024-10238-5","DOIUrl":"10.1007/s10930-024-10238-5","url":null,"abstract":"<div><p>The anaphase promoting complex (APC or cyclosome) is a major ubiquitin ligase that coordinates mitotic and G1 progression, acting as a major regulator of chromosome segregation. While the human APC contains fourteen subunits, it is yet to be explored in the pathogen <i>Entamoeba histolytica</i>. Our study reveals the existence of a single functional Apc10 homolog in <i>E</i>. <i>histolytica</i>, which acts as a processivity factor of ubiquitin ligase activity in human. A cDNA library generated from HM1:IMSS strain of <i>E</i>. <i>histolytica</i> was screened for interaction partners of EhApc10 in yeast two hybrid study. The novel interactor, a glycolytic enzyme, pyruvate phosphate dikinase (Ppdk) was found to interact with EhApc10 and further validated by in vitro assay. A comprehensive in silico study has emphasized the structural and functional aspects, encompassing physicochemical traits, predictive 3D structure modelling, validation of EhApc10-EhPpdk interaction through molecular docking and simulation. The interplay between a cell cycle protein and a glycolytic enzyme highlights the connection between cellular metabolism and the cell cycle regulatory mechanism. The study serves as the groundwork for future research on the non-mitotic role of APC beyond cell cycle.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"43 6","pages":"1104 - 1119"},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565297","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}