{"title":"Association Between Peripheral Blood Regulatory T Cell Content with Inflammatory Stress Response and Immune Response in Children with Sepsis.","authors":"Shaowen Huang, Xiaoqi Qiu","doi":"10.1007/s12033-024-01339-8","DOIUrl":"https://doi.org/10.1007/s12033-024-01339-8","url":null,"abstract":"<p><p>The study aims to analyze the correlation between Regulatory T(Treg) Cells and inflammatory stress response and immune response in sepsis patients. Sixty sepsis patients admitted between January 2021 and June 2023 were selected as the subjects and included in the observation group. During the same period, 80 healthy children who underwent physical examinations in the hospital were included in the control group. The Treg content, inflammatory mediators, and immune response biochemical indicators of two groups are compared. The Pearson correlation analysis verifies the correlation between Treg content and inflammatory stress response, and immune response. Treg content in the observation group exceeded that found in the control group (P < 0.05). Among the relevant biochemical indicators, Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Procalcitonin (PCT), and Hypersensitive C-reactive protein (hs-CRP) exceeded that found in healthy children (P < 0.05). The immunoglobulin IgA, IgM, and IgG in healthy children were below respective values in the control group (P < 0.05). The Pearson correlation data demonstrated that the peripheral blood Treg content in children with sepsis was positively related to inflammatory mediator indicators. It was negatively related with the immunoglobulin IgA, IgM, and IgG. In summary, when the Treg content in the peripheral blood of sepsis patients increases, it directly affects the body's inflammatory stress response and immune function.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801671","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":"Anti-aggregation Properties of the Mini-Peptides Derived from Alpha Crystallin Domain of the Small Heat Shock Protein, Tpv HSP 14.3.","authors":"Sema Zabcı, Semra Kocabıyık","doi":"10.1007/s12033-024-01332-1","DOIUrl":"https://doi.org/10.1007/s12033-024-01332-1","url":null,"abstract":"<p><p>The highly conserved alpha crystallin domain of the small heat shock proteins is essential for dimerization and also implicated in substrate interaction. In this study, we designed four novel mini-peptides from alpha crystallin domain of archaeal Small Heat Shock Protein Tpv HSP 14.3. Among the peptide designs, the mini-peptides <sub>38</sub>SDLVLEAEMAGFDKKNIKVS<sub>57</sub> and <sub>40</sub>LVLEAEMAGFD<sub>50</sub> overlapped to the sequences of β3-β4 region. The other two peptides <sub>77</sub>YIDQRVDKVYKVVKLPVE<sub>94</sub> and <sub>107</sub>GILTVRMK<sub>114</sub> correspond to β6-β7 region and β9, respectively. Functional activity of the peptides was evaluated by monitoring heat-induced aggregation of the model substrates alcohol dehydrogenase at 43 °C and citrate synthase at 45 °C. Our results showed that the (38-57) and the (77-94) fragments exhibited chaperone activity with both of the substrate proteins. The (40-50) fragment while exhibiting a noticeable protective effect (> 90%) when tested with citrate synthase showed an anti-chaperone property toward alcohol dehydrogenase. Unlike the (40-50) fragment, the (107-114) fragment did not show any chaperone activity with citrate synthase but exhibited the highest chaperone efficiency among four mini-peptides with alcohol dehydrogenase. The selectivity of the (40-50) and the (107-114) fragments in targeting the client proteins is most likely dependent on their surface hydrophobicity and/or charge as revealed by the sequence and exposed surface analyses.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792087","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}
Fizza Gul, Sajjad Ahmad, Kalsoom Khan, Rehana Masood, Farhan Siddique, Mehvish Bibi, Salma Mohammed Aljahdali, Mohammad Abdullah Aljasir, Tabarak Sabah Jassim, Dong-Qing Wei, Muhammad Irfan
{"title":"Identification of Novel Drug Molecules Against NS3-Like Helicase Enzyme of Alongshan Virus.","authors":"Fizza Gul, Sajjad Ahmad, Kalsoom Khan, Rehana Masood, Farhan Siddique, Mehvish Bibi, Salma Mohammed Aljahdali, Mohammad Abdullah Aljasir, Tabarak Sabah Jassim, Dong-Qing Wei, Muhammad Irfan","doi":"10.1007/s12033-024-01326-z","DOIUrl":"https://doi.org/10.1007/s12033-024-01326-z","url":null,"abstract":"<p><p>Alongshan virus (ALSV) is a novel tick-borne virus associated with human diseases. The ALSV is a segmented flavivirus from the family Flaviviridae. It is currently considered as tick-borne arbovirus. There is a high incidence of fever and headache among patients with ALSV infection, and some patients also present with fatigue, coma, depression, nausea, myalgia/arthralgia, and skin rashes. Neither a licensed vaccine nor a drug is currently available to treat ALSV. The development of new, practical, and innovative therapeutic approaches is needed to overcome the emergence of the pathogen. Research on drugs remains a complex, time-consuming, and expensive. The field of drug development has undergone a revolution due to the use of computational approaches, which provide several benefits that speed up and improve the process of developing novel drugs. The goal of this study is to identify novel drug-like molecules against NS3-like helicase enzyme of Alongshan virus. Using molecular docking, the binding potential of the top three ligands to the specified target was determined. Molecular dynamic simulations were used to identify the stabilities of the best-docked conformations followed by energy calculations and ADMET analysis. Three potential and promising compounds were identified by performing structure-based virtual screening of non-structural protein 3 (NS3) like helicase of Alongshan virus. The best-docked complexes identified through virtual screening were BDC-23169381, BDB-26412846, BDB-2641954. All these compounds had good pharmacokinetics characteristics and were identified as drug like.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792088","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}
Rongyanqi Wang, Wenzhi Hao, Yanqiu Sun, Bin Liang, Feifei Xue
{"title":"Identification of Oxidative Stress-Related Genes in Hyperlipidemia Based on Bioinformatic Analysis.","authors":"Rongyanqi Wang, Wenzhi Hao, Yanqiu Sun, Bin Liang, Feifei Xue","doi":"10.1007/s12033-024-01330-3","DOIUrl":"https://doi.org/10.1007/s12033-024-01330-3","url":null,"abstract":"<p><p>Oxidative stress (OS) is thought to mediate the processes of glycolipid disorders of a number of metabolic diseases and recent data suggest that OS may be involved in the pathophysiology of hyperlipidemia. The gene expression profiles of hyperlipidemia samples were downloaded from the Gene Expression Omnibus (GEO) database. Oxidative stress-related genes (ORGs) was the intersection of all valid data of discovery dataset and the ORGs in Genecards. The Differentially expressed genes (DEGs) between hyperlipidemia and control samples were obtained via \"limma\" R package, and differentially expressed oxidative stress-related genes (DEORGs) associated with hyperlipidemia were screened via OS gene sets. Gene Ontology (GO) and Kyoto encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were performed to study the biological function of DEORGs, and protein-protein interaction (PPI) network analysis was conducted to screen hub genes. Then we constructed microRNA (miRNA), transcription factor (TF) and drug component targets network to explain the regulatory mechanism of ORGs in hyperlipidemia. After screening and evaluating we took GSE1010 as the discovery dataset and the GSE13985 as the validation set. There were 395 ORGs and 14 DEORGs retained from the hyperlipidemia. GO and KEGG results showed that DEORGs were mostly related to OS and lipid metabolism. Then, we used miRNA, TF, and drug component targets network to reveal the regulatory mechanism of hub genes. Finally, we verified expression of DEGs and hub gene in validation set. Our study has further confirmed the relationships between OS and hyperlipidemia, providing oxidative stress-related hub genes with possible function analysis and pathways summarized. These molecules might play a crucial role in the progression of hyperlipidemia and serve as potential biomarkers and therapeutic targets, giving us additional insight into the genes and the mechanism linking the OS system and metabolic disorders. We have not only proved hyperlipidemia is associated with OS but also gave foundation and reference for future researches.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786319","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}
Subhashini Brahadeeswaran, Kiran Kumar Chitluri, Leema George, Venkatraman Manickam, Isaac Arnold Emerson, Ramasamy Tamizhselvi
{"title":"Scopoletin: A Validated Protector against Cerulein-induced Acute Pancreatitis & Associated Lung Injury by Regulating PPAR- γ \"A Multidimensional Approach\".","authors":"Subhashini Brahadeeswaran, Kiran Kumar Chitluri, Leema George, Venkatraman Manickam, Isaac Arnold Emerson, Ramasamy Tamizhselvi","doi":"10.1007/s12033-024-01327-y","DOIUrl":"https://doi.org/10.1007/s12033-024-01327-y","url":null,"abstract":"<p><p>Our previous study established the effectiveness of scopoletin (SC) in protecting mice against acute pancreatitis (AP) induced by cerulein and subsequent pulmonary injury. However, the precise molecular mechanisms underlying SC protective effects have yet to be elucidated. This research suggests that SC reduces the release of pro-inflammatory cytokines and nuclear factor kappa B (NF-κB) by activating the peroxisome proliferator-activated receptor γ (PPAR-γ) in mice suffering from AP. We observed the protective role of SC against the male Swiss mice with hourly intraperitoneal injections of cerulein (50 µg/kg) for six hours, followed by the administration of SC (10 mg/kg) one hour after AP induction, with or without the PPAR-γ antagonist GW9662 (0.3 mg/kg). The study exploration into the anti-inflammatory effects of SC revealed that a concentration of 25 µM enhanced the phagocytic clearance of dying pancreatic acinar cells by triggering the PPAR-γ signaling activation. Conversely, an in vitro assessment confirmed the presence of GW9662 counteracted the beneficial impact of SC on acinar cells. Molecular docking and simulation studies have shown that SC prompts significant structural changes in PPAR-γ. The in vivo, in vitro, and in silico analyses suggest that SC has potent anti-inflammatory properties that may be mediated by the activation of PPAR-γ signaling in cerulein-induced experimental pancreatitis.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770650","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":"Molecular Investigation of FIKK Kinase Family to Develop PCR-Based Diagnosis of Plasmodium falciparum.","authors":"M Rajendra Prasad, Vishal Trivedi","doi":"10.1007/s12033-024-01335-y","DOIUrl":"https://doi.org/10.1007/s12033-024-01335-y","url":null,"abstract":"<p><p>Accurate malaria diagnosis is crucial for effective disease management as different Plasmodium species require specific treatment regimens. Current detection methods have limitations related to sensitivity and specificity. This is mainly due to employing similar targets such as 18S rRNA, Pf-ldh, Pf-hrp-2, and aldolase with significant homology to human counterparts. Targeting Plasmodium fikk kinases that are unique to P. falciparum offers a novel approach for developing potential biomarkers. We have identified exclusive regions of fikk kinases using in-silico PCR and later validated our findings using in-vitro PCR. We observed exceptional sensitivity with our designed primers of the targeted fikk kinases, with the detection limit going as low as 10<sup>-5</sup> ng level of parasite DNA and 0.0003% parasitemia. The shortlisted primers also selectively identified P. falciparum in the presence of Plasmodium vivax or several other bacterial, viral, and fungal pathogens. Detection of mock patient samples indicates that the fikk-based PCR diagnosis is giving accurate results, and it is much better than the existing method. Thus, we show that the fikk kinases from P. falciparum are excellent targets for developing novel biomarkers with high sensitivity and specificity.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770649","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}
Molecular BiotechnologyPub Date : 2024-12-01Epub Date: 2023-12-12DOI: 10.1007/s12033-023-00978-7
Ting Ma, Xinguo Ge, Jie Zhu, Chengxin Song, Pinhao Wang, Jiali Cai
{"title":"Dioscin Impedes Proliferation, Metastasis and Enhances Autophagy of Gastric Cancer Cells via Regulating the USP8/TGM2 Pathway.","authors":"Ting Ma, Xinguo Ge, Jie Zhu, Chengxin Song, Pinhao Wang, Jiali Cai","doi":"10.1007/s12033-023-00978-7","DOIUrl":"10.1007/s12033-023-00978-7","url":null,"abstract":"<p><p>Gastric cancer (GC) is one of the most common cancers worldwide. Dioscin has been shown to have anti-cancer effects in GC. The aim of this study is to explore a novel mechanism of dioscin in repressing GC progression. Cell viability, proliferation, apoptosis and invasion were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry and transwell assays, respectively. Monodansylcadaverine (MDC) staining was used to assess cell autophagy. The expression of transglutaminase-2 (TGM2), ubiquitin-specific peptidase 8 (USP8) and autophagy-related proteins was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. A xenograft tumor model was established to investigate the function of dioscin in vivo. Dioscin inhibited GC cell proliferation and invasion, but induced apoptosis and autophagy. TGM2 was highly expressed in GC, and dioscin suppressed GC progression by decreasing the protein level of TGM2. Furthermore, USP8 positively regulated TGM2 expression, and TGM2 overexpression reversed the inhibitory effect of USP8 knockdown on GC cell progression. USP8 abated the effect of dioscin in GC cells. Dioscin decreased the protein level of TGM2 via regulating USP8. In addition, dioscin restrained GC tumor growth in vivo. Dioscin played an anti-cancer effect in GC by enhancing cancer cell autophagy via regulating the USP8/TGM2 pathway.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3700-3711"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138807732","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}
Molecular BiotechnologyPub Date : 2024-12-01Epub Date: 2023-11-02DOI: 10.1007/s12033-023-00952-3
Yu-Xiang Zhu, Qin Yang, You-Peng Zhang, Zhi-Gang Liu
{"title":"FGF2 Functions in H<sub>2</sub>S's Attenuating Effect on Brain Injury Induced by Deep Hypothermic Circulatory Arrest in Rats.","authors":"Yu-Xiang Zhu, Qin Yang, You-Peng Zhang, Zhi-Gang Liu","doi":"10.1007/s12033-023-00952-3","DOIUrl":"10.1007/s12033-023-00952-3","url":null,"abstract":"<p><p>Deep hypothermic circulatory arrest (DHCA) can protect the brain during cardiac and aortic surgery by cooling the body, but meanwhile, temporary or permanent brain injury may arise. H<sub>2</sub>S protects neurons and the central nervous system, especially from secondary neuronal injury. We aim to unveil part of the mechanism of H<sub>2</sub>S's attenuating effect on brain injury induced by DHCA by exploring crucial target genes, and further promote the clinical application of H<sub>2</sub>S in DHCA. Nine SD rats were utilized to provide histological and microarray samples, and further the differential expression analysis. Then we conducted GO and KEGG pathway enrichment analyses on candidate genes. The protein-protein interaction (PPI) networks were performed by STRING and GeneMANIA. Crucial target genes' expression was validated by qRT-PCR and western blot. Histological study proved DHCA's damaging effect and H<sub>2</sub>S's repairing effect on brain. Next, we got 477 candidate genes by analyzing differentially expressed genes. The candidate genes were enriched in 303 GO terms and 28 KEGG pathways. Then nine genes were selected as crucial target genes. The function prediction by GeneMANIA suggested their close relation to immunity. FGF2 was identified as the crucial gene. FGF2 plays a vital role in the pathway when H<sub>2</sub>S attenuates brain injury after DHCA. Our research provides more information for understanding the mechanism of H<sub>2</sub>S attenuating brain injury after DHCA. We infer the process might probably be closely associated with immunity.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3526-3537"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71425062","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":"HAGLR, A Long Non-coding RNA of Potential Tumor Suppressive Function in Clear Cell Renal Cell Carcinoma: Diagnostic and Prognostic Implications.","authors":"Abhishek Bardhan, Anwesha Banerjee, Dilip Kumar Pal, Amlan Ghosh","doi":"10.1007/s12033-023-00948-z","DOIUrl":"10.1007/s12033-023-00948-z","url":null,"abstract":"<p><p>Research works suggested the role of long non-coding RNAs (lncRNAs) in pathogenesis of clear cell renal cell carcinoma (ccRCC). lncRNA HAGLR is studied in several malignancies, but not in ccRCC. From The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) dataset, we analyzed molecular alterations of HAGLR and constructed a competitive endogenous RNA (ceRNA) network with related miRNAs and mRNAs. Gene Ontology analysis was done to identify important pathways enriched with HAGLR recovered mRNAs. Clinical importance of HAGLR and related mRNAs was assessed and, the impact of selected mRNA-encoding genes on tumor immune infiltration was studied using TIMER. HAGLR expression was reduced in ccRCC than in normal kidneys, and correlated significantly with gene promoter methylation. Low HAGLR level in tumors showed diagnostic potency, and was associated with clinicopathological parameters (stage/grade/metastasis) and poor patient survival. The HAGLR-associated ceRNA network constituted 13 miRNAs and 23 mRNAs differentially expressed in the TCGA-KIRC dataset. From HAGLR recovered mRNA-encoding genes, we developed a 5-gene (PAQR5, ARHGAP24, HABP4, PDLIM5, and RPS6KA2) prognostic signature in the training dataset and validated it in testing as well as entire datasets. The expression level of signature genes showed negative correlation with tumor infiltration of immune cells having adverse impact on ccRCC prognosis and also with tumor derived chemokines facilitating the infiltration. In conclusion, HAGLR seemed to play a tumor suppressive role in ccRCC. HAGLR and associated gene signature may have implementation in improving existing prognostic measure and developing effective immunotherapeutic strategies for ccRCC.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3485-3497"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89718945","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}
Molecular BiotechnologyPub Date : 2024-12-01Epub Date: 2023-11-13DOI: 10.1007/s12033-023-00951-4
Sayed Haidar Abbas Raza, Ruimin Zhong, Xiaoting Yu, Gang Zhao, Xiaoqun Wei, Hongtao Lei
{"title":"Advances of Predicting Allosteric Mechanisms Through Protein Contact in New Technologies and Their Application.","authors":"Sayed Haidar Abbas Raza, Ruimin Zhong, Xiaoting Yu, Gang Zhao, Xiaoqun Wei, Hongtao Lei","doi":"10.1007/s12033-023-00951-4","DOIUrl":"10.1007/s12033-023-00951-4","url":null,"abstract":"<p><p>Allostery is an intriguing phenomenon wherein the binding activity of a biological macromolecule is modulated via non-canonical binding site, resulting in synchronized functional changes. The mechanics underlying allostery are relatively complex and this review is focused on common methodologies used to study allostery, such as X-ray crystallography, NMR spectroscopy, and HDXMS. Different methodological approaches are used to generate data in different scenarios. For example, X-ray crystallography provides high-resolution structural information, NMR spectroscopy offers dynamic insights into allosteric interactions in solution, and HDXMS provides information on protein dynamics. The residue transition state (RTS) approach has emerged as a critical tool in understanding the energetics and conformational changes associated with allosteric regulation. Allostery has significant implications in drug discovery, gene transcription, disease diagnosis, and enzyme catalysis. Enzymes' catalytic activity can be modulated by allosteric regulation, offering opportunities to develop novel therapeutic alternatives. Understanding allosteric mechanisms associated with infectious organisms like SARS-CoV and bacterial pathogens can aid in the development of new antiviral drugs and antibiotics. Allosteric mechanisms are crucial in the regulation of a variety of signal transduction and cell metabolism pathways, which in turn govern various cellular processes. Despite progress, challenges remain in identifying allosteric sites and characterizing their contribution to a variety of biological processes. Increased understanding of these mechanisms can help develop allosteric systems specifically designed to modulate key biological mechanisms, providing novel opportunities for the development of targeted therapeutics. Therefore, the current review aims to summarize common methodologies that are used to further our understanding of allosteric mechanisms. In conclusion, this review provides insights into the methodologies used for the study of allostery, its applications in in silico modeling, the mechanisms underlying antibody allostery, and the ongoing challenges and prospects in advancing our comprehension of this intriguing phenomenon.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3385-3397"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92155362","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}