Current Proteomics最新文献

{"title":"The Relationship of Transposable Elements with Non-Coding RNAs in the Emergence of Human Proteins and Peptides","authors":"Rustam Nailevich Mustafin","doi":"10.2174/0115701646319572240805103747","DOIUrl":"https://doi.org/10.2174/0115701646319572240805103747","url":null,"abstract":"Transposable elements are the oldest structural and functional units that were formed during the emergence of life on Earth. The most ancient properties of transposable elements are the multifunctionality of their transcription and translation products and the formation of their many variants through processing, due to which transposable elements are key evolutionary sources of long non-coding RNAs, circular RNAs, microRNAs, proteins and peptides formation. Moreover, the same type of transposon can simultaneously serve as the source of the origin of all these molecules, providing the adaptive properties of living organisms, especially complex eukaryotes, including humans. The ancient ability of transposable elements for mutual integration due to their protein products interacting with DNA and RNA molecules, as well as for mutual regulation due to the functionality of their RNA, is the basis for the origin of many proteins and non-coding RNAs characterized by the same properties. This can explain the emergence of transcription factors from transposable elements, that is, proteins capable of interacting with the structures of DNA molecules due to the presence of specific amino acid sequences derived from transposable elements. This article presents facts about the origin during the evolution of many protein and non-- coding RNA genes from transposable elements. Specific proteins and peptides translated from long non-coding RNAs, pri-microRNAs and circular RNAs are described, which reflect the origin of non-coding RNAs from transposable elements in evolution. These proteins and peptides are promising tools for the treatment of viral infections and drug-resistant tumors, since, together with non-coding RNAs, they are involved in antiviral and antitumor responses.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"9 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217978","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":"Annotation-Based Study on Hypothetical Proteins in Bacteria Using Classification Features","authors":"Anchita Prasad, Prashanth Suravajhala, Vinod Kumar Nigam","doi":"10.2174/0115701646303687240805072304","DOIUrl":"https://doi.org/10.2174/0115701646303687240805072304","url":null,"abstract":"Background: Hypothetical proteins (HPs) are those proteins whose functions are unknown; therefore, the present study was carried out to predict similarity-based functionality of HPs in selected bacteria Streptomyces coelicolor A3(2) and Neisseria meningitidis. Methods: Annotation-based approaches using Pfam, orthology, String, Bi-directional Best Blast Hit, PSLpred, Subloc, Cello, homology modeling, and computational tools were used in evaluating the functionality of HPs. Results: Thirty-one domains in both bacterial species were retrieved based on the E-value score and compared with bacterial species already existing in databases. Statistical analysis was duly done to check which features performed well. Conclusion: Out of 31 HPs found in Streptomyces coleicolor strain A3(2), 14 domains were found to be uncharacterized in their functionality, while 2 uncharacterized domains in the case of Neisseria meningitidis were assigned a function on similarity-based approaches. The annotation of HPs is a challenge in bacteria as these are based on the similarity of proteins in other species.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"60 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217979","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":"Circulating Exosomes Studied by Label-free Proteomics Analysis Reveal Transition Signatures from Diabetes Mellitus to Diabetic Kidney Disease","authors":"Yue Yue, Yiying Tao, Jiaxin Wang, Shidi Zhao, Fan Zhao, Lei Shen, Ling Zhou","doi":"10.2174/0115701646309538240805093732","DOIUrl":"https://doi.org/10.2174/0115701646309538240805093732","url":null,"abstract":"Background: Diabetic kidney disease (DKD) is a common microvascular complication of diabetic mellitus (DM). At present, the early diagnosis of DKD mainly depends on microalbuminuria, which is prone to be affected by confounding factors such as urinary tract infections. Methods: To identify the more stable early diagnosis markers, the whole proteome in the circulating exosomes from controls, DM patients, and DKD patients was quantified by label-free proteomics analysis and then validated with parallel reaction monitoring. Results: Three hundred ninety-one quantitative proteins were detected, and the expression trends of 7 proteins in the validation phase were consistent with that in the discovery phase. The expression level assessment results revealed that the expression of EFEMP1 and ApoA4 in the DKD group was significantly higher than those in DM and controls. Correlation analysis showed that EFEMP1 and APOA4 were positively correlated with urinary microalbumin and urinary albumin creatinine ratio and had excellent diagnostic values for distinguishing DKD from DM and controls. Conclusions: ApoA4 and EFEMP1 could serve as the early diagnosis markers of DKD. These findings provide a possibility for the development of a clinical diagnostic index that can efficiently distinguish DKD from DM in the near future.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"10 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142227067","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":"Identification of Novel PBP2B Protein Inhibitors against Streptococcus pneumoniae in Marine Natural Products using an In-Silico Approach","authors":"Karthickeyan Chandrasekar, Parthasarathy Subbiah","doi":"10.2174/0115701646320388240805064243","DOIUrl":"https://doi.org/10.2174/0115701646320388240805064243","url":null,"abstract":"Background: The aim of this research is to identify marine natural compounds derived from green, red, and brown algae that might possibly inhibit the Penicillin-Binding Proteins (PBPs) protein, which is responsible for the development of antibiotic resistance in Streptococcus pneumoniae (mutated resistant 5204-PBP2B strain). We obtained this by using virtual screening and molecular docking. In AutoDock Vina and the Schrodinger suite software, we screened a library of marine natural chemicals and discovered four intriguing candidates that had strong binding affinities to the active region of the PBPs protein. Based on our findings, four naturally occurring marine chemicals show great promise as new inhibitors of S. pneumoniae 5204-PBP2B protein. These discoveries reveal important new information on the potential application of marine natural products as a source of new drugs to combat antibiotic resistance in Streptococcus pneumoniae and other bacterial infections. Methods: The 3318 compounds in the Comprehensive Marine Natural Products Database (CMNPD) derived from green algae (293 compounds), brown algae (1212 compounds) and red algae (1813 compounds) were taken into consideration for this study. Through virtual screening and molecular docking investigations, we found the optimum compounds for the Penicillin-Binding Proteins (PBPs) protein in Streptococcus pneumoniae. Utilizing AutoDock Vina and Schrodinger Suite software, the 5204-PBP2B protein selected for this investigation was examined. The structure and binding interaction have been displayed using PyMOL software. Results: Through virtual screening and molecular docking investigations for the 5204-PBP2B protein in Streptococcus pneumoniae, we were able to identify four marine natural products that are present in brown algae from the Comprehensive Marine Natural Products Database. Conclusion: The study has indicated that the main cause of bacterial resistance to antibiotics is 5204-PBP2B in S. pneumoniae. This study's methodology has been shown to be effective in identifying four strong inhibitors of the CMNPD. In this work, potent molecules from CMNPD compounds were screened using the 3D structure of mutated resistant 5204 strain, named 5204- PBP2B (PDB ID: 2WAE) of S. pneumoniae. Out of 3318 compounds that showed strong interactions with PBP2B, docking studies revealed that four of the compounds were inhibitory for the protein and could be used to treat PBP2B. These four marine products were selected as a result of our earlier research on Klebsiella pneumonia’s New Delhi metallo-β-lactamase-1 (NDM-1) protein. This study thus reveals the importance of marine natural products for improving the drug development process, as well as the ability of four marine products generated from brown algae to inhibit both the NDM-1 protein of Klebsiella pneumoniae and the 5204-PBP2B protein in Streptococcus pneumoniae. It is also possible to expand this approach by investigating how different receptor inhi","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"47 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217980","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 Study of Different Signal Peptides in Improvement of Recombinant Proteins Solubility in E. coli: A Mini-Review Article","authors":"Seyyed Soheil Rahmatabadi, Soudabeh Askari, Fatemeh Khademi, Bijan Soleymani","doi":"10.2174/0115701646305738240730113619","DOIUrl":"https://doi.org/10.2174/0115701646305738240730113619","url":null,"abstract":"In E. coli, the production of proteins as inclusion bodies (IBs) caused a decrease in the solubility and activity of these products. Diverse approaches and methods have been used by investigators to overcome this problem. The secretion of recombinant proteins into the periplasmic space by means of suitable signal peptides is a way to resolve these limitations for the production of recombinant proteins in a native form. Secretory production of recombinant proteins in bacterial hosts has many advantages and thus, it is a topic of interest. However, it is hard to achieve due to the difficulty of the process and the need for the choice of appropriate signal peptide for each host and protein. Based on the literature, different signal peptides have experimentally been applied to enhance the solubility of various recombinant proteins. It has been shown that the secretion efficiency of a given protein differs dramatically based on the type of the signal peptide that is attached to the protein. Therefore, the choice and alteration of signal peptides are the two crucial approaches for the improvement of a recombinant protein secretion that have been discussed in this review. Also, different factors affecting the expression and solubility of recombinant proteins have been discussed.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"57 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933831","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 Effect of N52R Mutation at the SPN-ARR Interface on the Conformational Dynamics of SHANK3","authors":"Hiba K. Almaadani, Venkata Satish Kumar Mattaparthi","doi":"10.2174/0115701646301703240730054408","DOIUrl":"https://doi.org/10.2174/0115701646301703240730054408","url":null,"abstract":"Background:: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition. The genetic basis of ASD involves numerous loci converging on neural pathways, particularly affecting excitatory synapses. SHANK3, an essential protein in the post-synaptic neurons, has been implicated in ASD, with mutations affecting its N-terminal, including the SPN domain. Objective: This study aims to investigate the impact of the N52R mutation on SHANK3 and assess the dynamics, stability, flexibility, and compactness of the N52R mutant compared to SHANK3 WT. Methods: Molecular dynamics simulations were conducted to investigate the structural dynamics of SHANK3 WT and the N52R mutant. The simulations involved heating dynamics, density equilibrium, and production dynamics. The trajectories were analyzed for RMSD, RMSF, Rg, hydrogen bond analysis, and secondary structure. Results: The simulations revealed that the N52R mutant disrupts the stability and folding of SHANK3, affecting intramolecular contacts between SPN and ARR. This disruption opens up the distance between SPN and ARR domains, potentially influencing the protein's interactions with partners, including αCaMKII and α-Fodrin. The altered conformation of the SPN-ARR tandem in the N52R mutant suggests a potential impact on dendritic spine shape and synaptic plasticity. Conclusion: The findings shed light on the structural consequences of the N52R mutation in SHANK3, emphasizing its role in influencing intramolecular interactions and potential effects on synaptic function. Understanding these molecular dynamics contributes to unraveling the intricate relationship between genetic variations in SHANK3 and clinical traits associated with ASD. Further investigations are warranted to explore the physiological implications of these structural alterations in vivo.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"370 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933832","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":"A Complete Sojourn of Monoclonal Antibodies: AI, Rare Diseases / Disorders And Immunotoxic Effects","authors":"Sonakshi Garg, Gurisha Garg, Preeti Patel, Ghanshyam Das Gupta, Balak Das Kurmi","doi":"10.2174/0115701646313765240610062419","DOIUrl":"https://doi.org/10.2174/0115701646313765240610062419","url":null,"abstract":": Monoclonal antibodies (mAbs) are magic bullets proved to be a wonder in the pharmaceutical as well as medical fields. These are produced by various methods like hybridoma technology, phage display technology, YAC technology, and transgenic animals and plants. Based on the percentage of animal origin, mAbs are divided into chimeric, murine, humanized, and fully human. This review covers the history and methods of mAb production, immunotoxicity (Immunosuppression, immunostimulant, autoimmunity, hypersensitivity) associated with mAbs, and targets of mAbs. It also compiles mAb production using AI, new modifications, and novel mAbs, with its various clinical trial information ensuring the use of mAbs in rare diseases and disorders.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"27 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141872320","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":"StemRegenin-1 Reverses Drug Resistance of MCF-7/ADR Cells via AhR/ABC Transports and AhR/UGTs Pathways","authors":"Yang Zhang, Yu-Chen Ma, Jue Song, Yong Jin, Yan-Ni Bao","doi":"10.2174/0115701646317215240712103448","DOIUrl":"https://doi.org/10.2174/0115701646317215240712103448","url":null,"abstract":"Objectives: Drug resistance reduces the antitumor efficacy of chemotherapy. Therefore, it is important to know how to reverse drug resistance. In this work, we investigated drug resistance reversal by StemRegenin-1(SR-1) in MCF-7/ADR cells and the mechanism by which it exerts its drug resistance effect. Methods: MTT test and protein blot were employed as the two main in vitro cell tests. The cells were treated with SR-1 and ADM to detect the changes in their proteomics, and then the effects of AhR downstream proteins, glucuronidase, and drug-resistant proteins were verified. The accumulation of ADM in the combined cells and its effect on the cell cycle were detected by flow cytometry. In vivo, a BALB/C mice xenograft test was conducted to observe the anti-tumor effect and side effects of the drug combination. Results: SR-1 combined with ADM inhibited cell proliferation and significantly decreased the expression of CYP1A1, UGT1A6, P-gP (ABCB1), and MRP1 (ABCC1). Furthermore, SR-1 caused apoptosis and cell cycle arrest. In vivo experiments showed that SR-1 significantly enhanced the antitumor effects of ADM and reduced the toxic effects of ADM. Conclusion: SR-1 inhibited AhR activity, decreased its downstream protein CYP1A1 and the expression of UGT1A6, P-gP, and MRP1 in MCF-7/ADR cells, and reversed drug resistance in MCF-7/ADR cells through AhR/ABC transports and AhR/UGTs pathways.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"98 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754007","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":"In silico Investigation on the Structural Insights into the Binding of Squalamine Inhibitor with Membrane-Bound Α-Synuclein","authors":"Dorothy Das, Priyam Bharadwaz, Venkata Satish Kumar Mattaparthi","doi":"10.2174/0115701646301714240703100842","DOIUrl":"https://doi.org/10.2174/0115701646301714240703100842","url":null,"abstract":"Background: Parkinson's disease (PD) and its associated symptoms are closely associated with the self-assembly of α-Synuclein (α-Syn). Squalamine is a naturally occurring chemical substance with established antiviral and anticancer properties, and its profound impact on the α- Syn aggregation both in vivo and in vitro is well studied. Examining its interaction with lipid vesicles, which are known to encourage nucleation, can signify the mechanism of action of squalamine. The squalamine molecule is believed to displace α-Syn from the surfaces of the lipid vesicles, therefore preventing the initial steps in the process of aggregation. Additionally, the squalamine molecule reduces the harmful effects of α-Syn oligomers in human neuroblastoma cells by preventing them from interacting with lipid membranes. Objective: The aim of this study was to perform computational investigation of the conformational changes of membrane-bound α-Syn in the presence of squalamine inhibitor molecule objective: Computational investigation of the conformational changes of membrane-bound α-Synuclein in the presence of squalamine inhibitor molecule Method: Molecular Dynamics (MD) trajectory analysis was carried out to study the structural change of the α-Syn-squalamine conformers as a function of simulation time. The percentage of the secondary structural components of the α-Syn-squalamine complex was determined. Optimization of small molecule inhibitors was carried out using Density Functional Theory (DFT) analysis. Additionally, the values of electrophilicity (ω), nucleophilicity (N), Electron affinity (EA), and ionization potential (IP) were calculated. Results: The docking of the α-Syn-squalamine complex revealed the binding site and the best structure was selected based on the highest docking vina score (-5.8), and the contact residues were listed. From the conformational snapshots of the α-Syn-squalamine complex, it was evident that the α-Syn remained stable, maintaining its integrity throughout the simulation. The α-helical content was found to be retained from the secondary structural content analysis. The ω and N of the squalamine molecule were calculated to be -0.84 and 3.25, respectively. Conclusion: Our findings suggest that in the presence of a squalamine inhibitor molecule, α-Syn adopts a helical conformation that ensures stability and may indicate that the squalamine molecule causes gradual displacement of α-Syn across different regions within the lipid membrane.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"33 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588403","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":"An Immunoinformatic Approach to Designing a Multi-epitope Vaccine against Helicobacter pylori with the VacA Toxin and BabA Adhesion","authors":"Viana Dayhimi, Fatemeh Ziadlou, Simin Nafian, Fatemeh Nafian","doi":"10.2174/0115701646302487240524103934","DOIUrl":"https://doi.org/10.2174/0115701646302487240524103934","url":null,"abstract":"Objective: Helicobacter pylori, as a carcinogen, has been related to the development of gastric cancer, particularly in developing countries. The main challenge with therapy is the recurrence of antibiotic-resistant bacteria, and vaccination is still a problem. Therefore, the objective of the current study was to rationally design a multi-epitope vaccine using two immunogenic proteins found in H. pylori. Methods: Promising epitopes for the Leb-binding adhesin A (BabA) and vacuolating cytotoxin (VacA) proteins were characterized through an immunoinformatics approach. Epitope-rich fragments were selected based on high-binding affinities with HLA classes I and II to be specifically presented to B and T lymphocytes and to selectively elicit both humoral and cellular immune responses. Results: Six constructs were planned by fusing these fragments in different arrangements with the help of GPGPG linkers. The most stable three-dimensional structure was found in Construct 6 during molecular dynamics. To improve immunogenicity and stability, an adjuvant called human β- defensin 2 (hBD-2) was joined to the N-terminus of Construct 6. Following molecular docking, the final vaccine reacted appropriately with each toll-like receptor 2 (TLR-2), TLR3, and TLR-4. The final DNA sequence was optimized for expression in E. coli K12 and in silico cloned into a pET-28a(+) plasmid. As a result of the vaccination in silico, substantial responses were developed against H. pylori. Conclusion: According to the immune response simulation, activated B and T lymphocytes and memory cell production increased. Macrophages and dendritic cells proliferated continuously, and IFN-γ and Cytokines, such as IL-2 were raised.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"23 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217981","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}