Biochemistry and Biophysics Reports最新文献

{"title":"Effects of the number of ethylene glycol units on the efficacy of novel complex I inhibitor 9bw","authors":"Kazuaki Sekimoto ,&nbsp;Hanaka Kinjo ,&nbsp;Mizuki Murakami ,&nbsp;Akiko Ohashi ,&nbsp;Rei Fukui ,&nbsp;Eri Nagasaki-Maeoka ,&nbsp;Yoshinori Inagaki ,&nbsp;Tadateru Takayama ,&nbsp;Kazuhiro Ikeda ,&nbsp;Ken-ichi Takayama ,&nbsp;Satoshi Inoue ,&nbsp;Motonori Tsuji ,&nbsp;Joe Otsuki ,&nbsp;Kyoko Fujiwara","doi":"10.1016/j.bbrep.2025.101981","DOIUrl":"10.1016/j.bbrep.2025.101981","url":null,"abstract":"<div><div>4′-Iodobiphenyl nonaethylene glycol ether (9bw) is a novel small molecule, composed of a biphenyl unit and 9 ethylene glycol (EG) units. Recently, we found that 9bw induces apoptosis in cancer cells by inhibiting mitochondrial respiratory complex I (CI) and accordingly reducing cellular ATP level. In addition, 9bw shows little effect on normal cells, suggesting that 9bw is a potential antitumor agent with few adverse effects. However, the exact molecular mechanisms by which 9bw acts on CI are still elusive. To clarify the molecular structure critical for 9bw′s function, we tested the function of 9bw analogues on human oral squamous cell carcinoma lines HSC4 and Ca9-22. The analogues were 4-hydroxy-4′-iodobiphenyl (HIOP), I-BP-EG3, I-BP-EG6, and I-BP-EG12 containing 0, 3, 6, and 12 EG units, respectively. Our results demonstrated that I-BP-EG6 and I-BP-EG12 inhibited CI to a similar extent as 9bw, whereas I-BP3 and HIOP showed no effect on CI activity. These observations indicate that the number of EG units is crucial for the activity of 9bw and its analogues. As high-performance liquid chromatography (HPLC) analysis demonstrated that both HIOP and I-BP-EG3 could be incorporated into mitochondria abundantly, the number of EG units probably affects CI inhibitory function of 9bw and its analogues rather than their efficacy to enter cell and mitochondria.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 101981"},"PeriodicalIF":2.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-silico analysis of nsSNPs in BCL-2 family proteins: Implications for colorectal cancer pathogenesis and therapeutics","authors":"Amanda Shen-Yee Kong ,&nbsp;Yong Chiang Tan ,&nbsp;Hin-Yee Thew ,&nbsp;Kok-Song Lai ,&nbsp;Swee-Hua Erin Lim ,&nbsp;Sathiya Maran ,&nbsp;Hwei-San Loh","doi":"10.1016/j.bbrep.2025.101957","DOIUrl":"10.1016/j.bbrep.2025.101957","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is a multifaceted disease characterized by abnormal cell proliferation in the colon and rectum. The <em>BCL-2</em> family proteins are implicated in CRC pathogenesis, yet the impacts of genetic variations within these proteins remains elusive. This <em>in-silico</em> study employs diverse sequence- and structure-based bioinformatics tools to identify potentially pathogenic nonsynonymous single nucleotide polymorphisms (nsSNPs) in <em>BCL-2</em> family proteins. Leveraging computational tools including SIFT, PolyPhen-2, SNPs&amp;GO, PhD-SNP, PANTHER, and Condel, 94 nsSNPs were predicted as deleterious, damaging, and disease-associated by at least five tools. Stability analysis with I-Mutant2.0, MutPred, and PredictSNP further identified 31 nsSNPs that reduce protein stability. Conservation analysis highlighted highly functional, exposed variants (rs960653284, rs758817904, rs1466732626, rs569276903, rs746711568, rs764437421, rs779690846, and rs2038330314) and structural, buried variants (rs376149674, rs1375767408, rs1582066443, rs367558446, rs367558446, rs1319541919, and rs1370070128). To explore the functional effects of these mutations, molecular docking and molecular dynamics simulations were conducted. G233D (rs376149674) and R12G (rs960653284) mutations in the <em>BCL2</em> protein exhibited the greatest differences in docking scores with <span>d</span>-α-Tocopherol and Tocotrienol, suggesting enhanced protein-ligand interactions. The simulations revealed that <span>d</span>-α-Tocopherol and Tocotrienol (strong binders) contributed to greater stability of <em>BCL-2</em> family proteins, while Fluorouracil, though weaker, still demonstrated selective binding stability. This work represents the first comprehensive computational analysis of functional nsSNPs in <em>BCL-2</em> family proteins, providing insights into their roles in CRC pathogenesis. While these findings demand experimental validation, they hold great promise for guiding future large-scale population studies, facilitating drug repurposing efforts, and advancing the development of targeted diagnostic and therapeutic modalities for CRC.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 101957"},"PeriodicalIF":2.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An association study of SERPINA1 gene polymorphisms with the risk of metabolic dysfunction-associated steatotic liver disease In an Iranian population: A preliminary case-control study","authors":"Samira Abdollahi ,&nbsp;Abbas Sahebghadam Lotfi ,&nbsp;Ramin Saravani ,&nbsp;Hamed Taheri","doi":"10.1016/j.bbrep.2025.101974","DOIUrl":"10.1016/j.bbrep.2025.101974","url":null,"abstract":"<div><h3>Background</h3><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a type of fat accumulation in the liver that can lead to cirrhosis and chronic liver disease. MASLD is recognized as the most frequent of liver-associated deaths worldwide. The <em>SERPINA1</em> gene encodes a serine protease protein that plays a pivotal role in the pathogenesis of liver deficiencies. In this study, we aimed to evaluate the genetic association between rs6647 (M1), rs709932 (M2), and rs1303 (M3) variants in the <em>SERPINA1</em> gene and the risk of MASLD in an Iranian population.</div></div><div><h3>Methods</h3><div>In this case-control study, 120 patients affected by MASLD and 120 healthy subjects participated. The Nephelometry system measured serum levels of α1-antitrypsin (A1AT). Biochemical tests were conducted to assess serum levels of blood parameters using commercially available kits. DNA extraction was performed using the salting-out method, followed by the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method for genotyping. Statistical analysis was performed by SPSS v16.0.</div></div><div><h3>Results</h3><div>The findings showed that the rs6647 G allele significantly increased the risk of MASLD. The G allele in codominant, dominant, and over-dominant models caused an increase in the risk of MASLD. Additionally, the rs709932 T allele was more frequent among patients compared to healthy subjects and significantly enhanced the risk of MASLD. The T allele in the codominant and recessive models indicated a high risk for MASLD in our population. The G allele of rs1303 caused an enhancement in the mean serum levels of A1AT in the MASLD group.</div></div><div><h3>Conclusions</h3><div>Our results show an association between <em>SERPINA1</em> gene variants and the risk of MASLD. The rs6647 (M1) and rs709932 (M2) variants of the <em>SERPINA1</em> gene increased the risk of disorder in our population.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 101974"},"PeriodicalIF":2.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lack of significant ganglioside changes in Slc17a5 heterozygous mice: Relevance to FSASD and Parkinson's disease","authors":"Marya S. Sabir ,&nbsp;Mahin S. Hossain ,&nbsp;Laura Pollard ,&nbsp;Marjan Huizing ,&nbsp;William A. Gahl ,&nbsp;Frances M. Platt ,&nbsp;May Christine V. Malicdan","doi":"10.1016/j.bbrep.2025.101979","DOIUrl":"10.1016/j.bbrep.2025.101979","url":null,"abstract":"<div><div>Large population-based studies of Parkinson's disease (PD) have identified susceptibility genes, including <em>SLC17A5</em>. Biallelic mutations in <em>SLC17A5</em>, encoding the lysosomal sialic acid transporter sialin, cause the rare neurodegenerative disease, free sialic acid storage disorder (FSASD). To explore a potential biochemical link between FSASD and PD, we investigated ganglioside concentrations in a novel mouse model harboring the <em>Slc17a5</em> p.Arg39Cys (p.R39C) variant. Our analysis revealed no significant alterations in ganglioside concentrations in heterozygous p.R39C mice, warranting further studies into other potential links between PD and sialin defects.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 101979"},"PeriodicalIF":2.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eco-friendly synthesis of copper nanoparticles by using Ralstonia sp. and their antibacterial, anti-biofilm, and antivirulence activities","authors":"Narges Vakili ,&nbsp;Morahem Ashengroph ,&nbsp;Aram Sharifi ,&nbsp;Musa Moetasam Zorab","doi":"10.1016/j.bbrep.2025.101978","DOIUrl":"10.1016/j.bbrep.2025.101978","url":null,"abstract":"<div><div>Biosynthesized nanoparticles (NPs) created through environmentally friendly and low-toxicity methods show great potential for various nanotechnology applications. In particular, copper nanoparticles (Cu-NPs) are promising for medical uses. This study aims to explore the eco-friendly synthesis of Cu-NPs and their potential as a novel strategy to combat antimicrobial resistance. Cu-NPs were synthesized using <em>Ralstonia</em> sp. KF264453 and characterized with techniques including ultraviolet–visible (UV–Vis) spectroscopy, field emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDX), dynamic light scattering (DLS), zeta potential analysis, X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). The antibacterial properties of the NPs and their synergistic effects with common antibiotics were assessed. The study also investigated their impact on bacterial cell membrane disruption, biofilm formation, efflux pump activity, and motility. UV–Vis analysis indicated a significant absorption peak at 552 nm, confirming surface plasmon resonance (SPR) for Cu-NPs. FESEM images revealed predominantly spherical NPs with an average size of 69.7 nm. DLS measurements indicated a hydrodynamic diameter of 78.2 nm due to stabilizing biomolecules. A zeta potential of −5.1 mV suggested moderate colloidal stability, suitable for short-term biomedical applications. XRD analysis confirmed a face-centered cubic (FCC) crystalline structure with an average crystallite size of 45 nm. FT-IR spectra detected functional groups, indicating that proteins, carbohydrates, lipids, and amino acids may have contributed to the synthesis and stabilization of the NPs. Cu-NPs showed notable antibacterial efficacy, with minimum inhibitory concentrations (MIC) between 0.625 and 5 μg/mL and minimum bactericidal concentrations (MBC) ranging from 5 to 20 μg/mL. They improved the effectiveness of penicillin and cefixime, enhanced membrane permeability, inhibited biofilm formation, disrupted efflux pump activity in <em>Staphylococcus aureus</em> SA-1199B, and decreased swarming motility in <em>Pseudomonas aeruginosa</em>. Cu-NPs demonstrate strong antimicrobial activity, inhibit biofilm formation and efflux pump function, and enhance the effectiveness of conventional antibiotics. While they show promise in combating antimicrobial resistance, further research is needed to assess their clinical potential and safety for medical use.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 101978"},"PeriodicalIF":2.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa-miR-31-3p targets CLDN8 to compromise skin barrier integrity in psoriasis","authors":"Yunhua Tu ,&nbsp;Li Wang ,&nbsp;Lijun An ,&nbsp;Li He","doi":"10.1016/j.bbrep.2025.101976","DOIUrl":"10.1016/j.bbrep.2025.101976","url":null,"abstract":"<div><div>Skin barrier dysfunction in psoriasis has emerged as a significant concern, yet the underlying molecular mechanisms remain incompletely understood. This study investigates the role of hsa-miR-31-3p in regulating skin barrier function through its interaction with claudin-8 (CLDN8) in psoriasis. Through analysis of clinical samples and public datasets, we observed significantly impaired skin barrier function in psoriasis patients, characterized by increased transepidermal water loss and decreased stratum corneum hydration. Notably, CLDN8 expression was markedly downregulated in psoriatic lesions, while hsa-miR-31-3p levels were elevated. Bioinformatics analysis and molecular studies revealed that hsa-miR-31-3p directly targets the 3′UTR of CLDN8, leading to its downregulation. In vitro experiments demonstrated that both CLDN8 knockdown and hsa-miR-31-3p overexpression compromised the permeability barrier in keratinocytes. Furthermore, in an imiquimod-induced psoriasis mouse model, administration of mmu-miR-31-3p antagomir effectively ameliorated skin barrier damage, reduced inflammatory manifestations, and restored CLDN8 expression. These findings unveil a novel mechanism whereby hsa-miR-31-3p regulates skin barrier function through CLDN8 in psoriasis, suggesting potential therapeutic strategies targeting this pathway for psoriasis treatment.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 101976"},"PeriodicalIF":2.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico studies to understand the interactions of flavonoid inhibitor with nsp12-RNA dependent RNA polymerase of SARS-CoV-2 and its homologs","authors":"Shamiya Anwar Kizhakkiniyakath,&nbsp;Tejaswini Choudhury,&nbsp;Madhan Vishal Rajan,&nbsp;Sagar Rathee,&nbsp;Basant Meena ,&nbsp;Gururao Hariprasad","doi":"10.1016/j.bbrep.2025.101975","DOIUrl":"10.1016/j.bbrep.2025.101975","url":null,"abstract":"<div><h3>Aim</h3><div>COVID 19 continues to be a major health concern. RNA dependent RNA polymerase of <em>SARS-CoV-2</em> which is crucial for replication is therefore a potential drug target.</div></div><div><h3>Methodology</h3><div>Based on experimental structures of RdRp from <em>SARS-CoV-2</em>, computational models were generated of its homologs from <em>SARS-C</em><em>o</em><em>V-1</em>, <em>MERS</em> and <em>Bat</em>. <em>SARS CoV-2</em> RdRp was used for virtual screening at nucleotide binding site with molecule from COCONUT Natural Products database using Glide. Complexes with the top inhibitor molecule were modelled using Discovery Studio and Desmond suite of programs.</div></div><div><h3>Results</h3><div><em>SARS-CoV-2</em> RdRp has a minimum of 80 % sequence similarity with its homologs, with the secondary structural elements, catalytic residues and metal binding residues being conserved. Certain residue variations in <em>SARS-CoV-2</em> RdRp seems to be responsible for the stability of the enzyme. Docking and simulation studies showed that a flavonoid molecule with Coconut ID: CNP0127177.0 (HHF318) has binding affinity in low nano-molar range against RdRp from <em>SARS-CoV-2</em> which was comparable or better than currently used inhibitors. This affinity stems from cationic-π with Arg555, and π-stacking interactions with a nucleobase of RNA. Molecule also engages with other residues that are crucial for its functions. This flavonoid molecule has similar physio-chemical properties like ATP towards <em>SARS-CoV-2</em> RdRp, and has low potency for human ATP binding proteins.</div></div><div><h3>Conclusion</h3><div>HHF318 is a potential inhibitor of <em>SARS-CoV-2</em> RdRp with good potency, specificity and pharmacokinetic properties for it to be developed as a drug candidate for COVID19.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 101975"},"PeriodicalIF":2.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenome editing-mediated restoration of FBN1 expression by demethylation of CpG island shore in porcine fibroblasts","authors":"Rio Miyadai ,&nbsp;Shiori Hinata ,&nbsp;Yuya Amemiya ,&nbsp;Satori Shigematsu ,&nbsp;Kazuhiro Umeyama ,&nbsp;Hiroshi Nagashima ,&nbsp;Kenji Yamatoya ,&nbsp;Jun Ohgane","doi":"10.1016/j.bbrep.2025.101973","DOIUrl":"10.1016/j.bbrep.2025.101973","url":null,"abstract":"<div><div>Fibrillin-1, an extracellular matrix protein encoded by the <em>FBN1</em> gene, is crucial for maintaining connective tissue integrity. Mutations in <em>FBN1</em> result in haploinsufficiency, leading to Marfan syndrome, in which the expression of functional <em>FBN1</em> is correlated with disease onset and severity. Recent studies suggest that <em>FBN1</em> expression is modulated by DNA methylation, particularly within the CpG island shores of its promoter region. In porcine models, <em>FBN1</em> mRNA levels have been found to correlate with the proportion of hypomethylated alleles in the CpG island shore region. In this study, we employed epigenome editing using the dCas9-TET1 system to induce targeted DNA demethylation within the <em>FBN1</em> CpG island shore, which became hypermethylated after a prolonged culture of porcine fetal fibroblast cells. This approach effectively reduced methylation in the targeted region, and cells expressing the dCas9-TET1 system maintained hypomethylation across multiple passages. Critically, DNA demethylation of the <em>FBN1</em> CpG island shore restored <em>FBN1</em> expression in heterozygous <em>FBN1</em> knockout fibroblasts, which developed stochastic hypermethylation after extended culture. These findings highlight the potential of DNA methylation manipulation to restore <em>FBN1</em> expression in cells with a haploinsufficient genetic background.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 101973"},"PeriodicalIF":2.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143593789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of lncRNA-protein interactions associated with Prostate cancer and Androgen receptors by molecular docking simulations","authors":"Barkha Khilwani ,&nbsp;Bhumandeep Kour ,&nbsp;Nidhi Shukla ,&nbsp;Sugunakar Vuree ,&nbsp;Abdul S. Ansari ,&nbsp;Nirmal K. Lohiya ,&nbsp;Prashanth Suravajhala ,&nbsp;Renuka Suravajhala","doi":"10.1016/j.bbrep.2025.101959","DOIUrl":"10.1016/j.bbrep.2025.101959","url":null,"abstract":"<div><div>Long non-coding RNA (lncRNAs) are known to be implicated in pathogenesis of a broad spectrum of malignancies. These are found to have a significant role as signal transduction mediators in cancer signaling pathways. Prostate Cancer (PCa) is emerging with increasing cases worldwide even as advanced approaches in clinical diagnosis and treatment of PCa are still challenging to address. To enhance patient stratification, there is an indefatigable need to understand risk that can allow new approaches of treatment based on prognosis. While PCa is known to have mediated androgen receptor (AR) stimulation, the latter plays a critical role in regulating transcription of genes via nuclear translocation which in turn leads to response to androgens. LncRNAs have been implicated in developing clinical diagnostic and prognostic biomarkers in a broad spectrum of cancers. In our present study, 12 lncRNAs identified from clinical samples from our erstwhile PCa patients were docked with PCa and AR targeted 36 proteins. We identified three lncRNAs, <em>viz.</em> SCARNA10, NPBWR1, ANKRD20A9P are common between the targeted proteins and discern that SCARNA10 lncRNA could serve as a prognostic signature for PCa and AR biogenesis. We also sought to check the coding potential of interfacial residues associated with lncRNA docking sites.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 101959"},"PeriodicalIF":2.3,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive in silico characterization of nonsynonymous SNPs in the human ezrin (EZR) gene and their role in disease pathogenesis","authors":"Sadia Akter ,&nbsp;Mohtasim Fuad ,&nbsp;Zimam Mahmud,&nbsp;Sonia Tamanna,&nbsp;Mohammad Sayem,&nbsp;Khalid Hasan Raj,&nbsp;Md. Zakir Hossain Howlader","doi":"10.1016/j.bbrep.2025.101972","DOIUrl":"10.1016/j.bbrep.2025.101972","url":null,"abstract":"<div><div>Ezrin (EZR) is a crucial linker between the actin cytoskeleton and the plasma membrane. It interacts with proteins involved in cancer-related signaling pathways. To assess the impact of nonsynonymous single nucleotide polymorphisms (nsSNPs) on EZR structure and function, we employed bioinformatics tools (SIFT, PolyPhen-2, PROVEAN, PhD-SNP, SNPs&amp;GO, SuSPect, and FATHMM) and identified deleterious variants. Stability analyses using MUpro, mCSM, I-Mutant 2.0, and DynaMut2 revealed six destabilizing nsSNPs (F240S, H288D, I248T, L59Q, L125S, and L225P). Structural modeling using HOPE, MutPred2, AlphaFold, Swiss-Model, and protein-protein docking using HADDOCK 2.4 assessed the impact on the EZR-EBP50 complex. Binding free energy calculations, salt bridge analysis, and interface residue mapping further confirmed that the L225P, F240S, and I248T mutations significantly impaired EZR-EBP50 interaction, potentially disrupting key signaling pathways. Molecular dynamics simulations indicated that mutant EZR proteins exhibited reduced stability, flexibility, and hydrogen bonding. This first comprehensive in silico analysis of EZR highlights pathogenic nsSNPs that may contribute to disease progression. These findings provide a foundation for experimental validation and may inform targeted therapies for EZR-related pathologies.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 101972"},"PeriodicalIF":2.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}