Journal of Biomolecular Structure & Dynamics最新文献_第5页

Computational study of the mechanism of binding of antifungal icofungipen in the active site of eukaryotic isoleucyl tRNA synthetase from Candida albicans. 抗真菌药物icofungipen与真核异亮氨酰tRNA合成酶活性位点结合机制的计算研究。

IF 2.4 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-08-01 Epub Date: 2024-03-06 DOI: 10.1080/07391102.2024.2323143

Shilpi Chowdhury, Nilashis Nandi

{"title":"Computational study of the mechanism of binding of antifungal icofungipen in the active site of eukaryotic isoleucyl tRNA synthetase from Candida albicans.","authors":"Shilpi Chowdhury, Nilashis Nandi","doi":"10.1080/07391102.2024.2323143","DOIUrl":"10.1080/07391102.2024.2323143","url":null,"abstract":"The eukaryotic fungal species Candida albicans is a critical infective pathogenic agent. The β-amino acid, Icofungipen, is an effective inhibitor of Candida albicans. Icofungipen binds at the active site of the isoleucyl tRNA synthetase (IleRS) from Candida albicans (CaIleRS) and halts protein translation in fungus. In the present work, we have investigated the mechanism of binding of Icogungipen (abbreviated as IFP). Molecular dynamics (MD) simulations show that the carboxylic acid group of IFP in the CaIleRS: IFP complex is more oriented towards the Connective Polypeptide (CP) core loop compared to the carboxylic acid group of Ile in the CaIleRS: Ile complex. The Arg 410 of the CP core loop near the substrate is extended towards the IFP. Due to the difference in the conformation of residues of the CP core loop, the KMSKR loop is more proximal to the CP core loop in CaIleRS: IFP. The editing domain which is covalently linked with the CP core loop in the CaIleRS: IFP complex is also oriented in such a way that the active site cavity is narrow and longer. The metadynamics calculation shows that the IFP is trapped in a deeper potential well compared to Ile which is due to the effective closure of the gateway of the active site by KMSKR and CP core loop. The thin, long shape of the active site and the closed gate of the active site in CaIleRS: IFP complex is responsible for the effective capture of IFP relative to Ile in the active site.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6137-6147"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unraveling the ligand specificity and promiscuity of the Staphylococcus aureus NorA efflux pump: a computational study. 揭示金黄色葡萄球菌 NorA 外排泵的配体特异性和杂交性：一项计算研究。

IF 2.4 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-08-01 Epub Date: 2024-03-18 DOI: 10.1080/07391102.2024.2326670

Esra Büşra Işık, Onur Serçinoğlu

{"title":"Unraveling the ligand specificity and promiscuity of the Staphylococcus aureus NorA efflux pump: a computational study.","authors":"Esra Büşra Işık, Onur Serçinoğlu","doi":"10.1080/07391102.2024.2326670","DOIUrl":"10.1080/07391102.2024.2326670","url":null,"abstract":"Staphylococcus aureus, a gram-positive bacterial pathogen, develops antibiotic resistance partly through enhanced activity of transmembrane multi-drug efflux pump proteins like NorA. Being a prominent member of the Major Facilitator Superfamily (MFS), NorA transports various small molecules including hydrophilic fluoroquinolone antibiotics across the cell membrane. Intriguingly, NorA is inhibited by a structurally diverse set of small molecule inhibitors as well, indicating a highly promiscuous ligand/inhibitor recognition. Our study aims to elucidate the structural facets of this promiscuity. Known NorA inhibitors were grouped into five clusters based on chemical class and docked into ligand binding pockets on NorA conformations generated via molecular dynamics simulations. We discovered that several key residues, such as I23, E222, and F303, are involved in inhibitor binding. Additionally, residues I244, T223, F303, and F140 were identified as prominent in interactions with specific ligand clusters. Our findings suggest that NorA's substrate binding site, encompassing residues aiding ligand recognition based on chemical nature, facilitates the recognition of chemically diverse ligands. This insight into NorA's structural promiscuity in ligand recognition not only enhances understanding of antibiotic resistance mechanisms in S. aureus but also sets the stage for the development of more effective efflux pump inhibitors, vital for combating multidrug resistance.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6159-6170"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction. 更正。

IF 2.4 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-08-01 Epub Date: 2024-08-05 DOI: 10.1080/07391102.2024.2385611

引用次数: 0

Evaluation of the efficacy of marine natural products against PARP-1/2 proteins in high-grade serous ovarian cancer: insights into MD and SMD simulations. 评估海洋天然产品对高级别浆液性卵巢癌 PARP-1/2 蛋白的疗效：MD 和 SMD 模拟的启示。

IF 2.4 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-08-01 Epub Date: 2024-06-17 DOI: 10.1080/07391102.2024.2335290

Sridhar Priyankha, Muthuramalingam Prakash

{"title":"Evaluation of the efficacy of marine natural products against PARP-1/2 proteins in high-grade serous ovarian cancer: insights into MD and SMD simulations.","authors":"Sridhar Priyankha, Muthuramalingam Prakash","doi":"10.1080/07391102.2024.2335290","DOIUrl":"10.1080/07391102.2024.2335290","url":null,"abstract":"High-grade serous ovarian cancer (HGSOC) is the most malignant and ubiquitous phenotype of epithelial ovarian cancer. Originating in the fallopian tubes and rapidly spreading to the ovaries, this highly heterogeneous disease is a result of serous tubal intraepithelial carcinoma. The proteins known as poly(ADP-ribose) polymerase (PARP) aid in the development of HGSOC by repairing the cancer cells that proliferate and spread metastatically. By using molecular docking to screen 1100 marine natural products (MNPs) from different marine environments against PARP-1/2 proteins, prominent PARP inhibitors (PARPi) were identified. Four compounds, alisiaquinone A, alisiaquinone C, ascomindone D and (+)-zampanolide referred to as MNP-1, MNP-2, MNP-3 and MNP-4, respectively, were chosen based on their binding affinity towards PARP-1/2 proteins, and their bioavailability and drug-like qualities were accessed using ADMET analysis. To investigate the structural stability and dynamics of these complexes, molecular dynamics simulations were performed for 200 ns. These results were compared with the complexes of olaparib (OLA), a PARPi that has been approved by the FDA for the treatment of advanced ovarian cancer. We determined that MNP-4 exhibited stronger binding energies with PARP-1/2 proteins than OLA by using MM/PBSA calculations. Hotspot residues from PARP-1 (E883, M890, Y896, D899 and Y907) and PARP-2 (Y449, F450, A451, S457 and Y460) showed strong interactions with the compounds. To comprehend the unbinding mechanism of MNP-4 complexed with PARP-1/2, steered molecular dynamics (SMD) simulations were performed. We concluded from the free energy landscape (FEL) map that PARP-1/2 are well-stabilised when the compound MNP-4 is bound rather than being pulled away from its binding pockets. This finding provides significant evidence regarding PARPi, which could potentially be employed in the therapeutic treatment of HGSOC.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"7031-7045"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Haplotype analysis, regulatory elements and docking simulation of structural models of different AT3 copies in the genus Capsicum. 辣椒属不同 AT3 副本的单倍型分析、调控要素和结构模型的对接模拟。

IF 2.4 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-08-01 Epub Date: 2024-02-14 DOI: 10.1080/07391102.2024.2317991

Eduardo Burgos-Valencia, Ileana Echevarría-Machado, Gustavo Ortega-Lule, Fátima Medina-Lara, Federico García-Laynes, Manuel Martínez-Estévez, José Narváez-Zapata

{"title":"Haplotype analysis, regulatory elements and docking simulation of structural models of different AT3 copies in the genus Capsicum.","authors":"Eduardo Burgos-Valencia, Ileana Echevarría-Machado, Gustavo Ortega-Lule, Fátima Medina-Lara, Federico García-Laynes, Manuel Martínez-Estévez, José Narváez-Zapata","doi":"10.1080/07391102.2024.2317991","DOIUrl":"10.1080/07391102.2024.2317991","url":null,"abstract":"Capsaicinoids are responsible for the pungency in Capsicum species. These are synthesized by the Capsaicin synthase (CS) encoded by the AT3 gene, which catalyzes the transference of an acyl moiety from a branched-chain fatty acid-CoA ester to the vanillylamine to produce capsaicinoids. Some AT3 gene copies have been identified on the Capsicum genome. The absence of capsaicinoid in some nonpungent accessions is related to mutant AT3 alleles. The differences between CS protein copies can affect the tridimensional structure of the protein and the affinity for its substrates, and this could affect fruit pungency. This study characterized 32 AT3 sequences covering Capsicum pungent and non-pungent accessions. These were clustered in AT3-D1 and AT3-D2 groups and representative sequences were analyzed. Genomic upstream analysis shows different regulatory elements, mainly responsive to light and abiotic stress. AT3-D1 and AT3-D2 gene expression was confirmed in fruit tissues of C. annuum. Amino acid substitutions close to the predictable HXXXD and DFGWG motifs were also identified. AT3 sequences were modeled showing a BAHD acyltransferase structure with two connected domains. A pocket with different shape, size and composition between AT3 models was found inside the protein, with the conserved motif HXXXD exposed to it, and a channel for their accessibility. CS substrates exhibit high interaction energies with the His and Asp conserved residues. AT3 models have different interaction affinities with the (E)-8-methylnon-6-enoyl-CoA, 8-methylnonanoyl-CoA and vanillylamine substrates. These results suggested that AT3-D1 and AT3-D2 sequences encode CS enzymes with different regulatory factors and substratum affinities.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6869-6882"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular insights into inhibiting effects of lignin on cellulase investigated by molecular dynamics simulation. 通过分子动力学模拟研究木质素对纤维素酶抑制作用的分子见解。

IF 2.4 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-08-01 Epub Date: 2024-03-18 DOI: 10.1080/07391102.2024.2328738

Zhenjuan Chen, Qingwen Shi, Tengfei Zhao, Yuxi Liu, Jinhong Hao, Zhijian Li, Lulu Ning

{"title":"Molecular insights into inhibiting effects of lignin on cellulase investigated by molecular dynamics simulation.","authors":"Zhenjuan Chen, Qingwen Shi, Tengfei Zhao, Yuxi Liu, Jinhong Hao, Zhijian Li, Lulu Ning","doi":"10.1080/07391102.2024.2328738","DOIUrl":"10.1080/07391102.2024.2328738","url":null,"abstract":"The hydrolysis of lignocellulose into fermentable monosaccharides using cellulases represents a critical stage in lignocellulosic bioconversion. However, the inactivation of cellulase in the presence of lignin is attributed to the high cost of biofinery. To address this challenge, a comprehensive investigation into the structure-function relationship underlying lignin-driven cellulase inactivation is essential. In this study, molecular docking and molecular dynamics (MD) simulations were employed to explore the impacts of lignin fragments on the catalytic efficiency of cellulase at the atomic level. The findings revealed that soluble lignin fragments and cellulose could spontaneously form stable complexes with cellulase, indicating a competitive binding scenario. The enzyme's structure remained unchanged upon binding to lignin. Furthermore, specific amino acid residues have been identified as involved in interactions with lignin and cellulose. Hydrophobic interactions were found to dominate the binding of lignin to cellulase. Based on the mechanisms underlying the interactions between lignin fragments and cellulase, decreased hydrophobicity and change in the charge of lignin may mitigate the inhibition of cellulase. Furthermore, site mutations and chemical modification are also feasible to improve the efficiency of cellulase. This study may contribute valuable insights into the design of more lignin-resistant enzymes and the optimization of lignocellulosic pretreatment technologies.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6927-6939"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reinventing PARP1 inhibition: harnessing virtual screening and molecular dynamics simulations to identify repurposed drugs for anticancer therapeutics. 重新发明PARP1抑制：利用虚拟筛选和分子动力学模拟来识别抗癌治疗的重新用途药物。

IF 2.4 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-08-01 Epub Date: 2025-03-26 DOI: 10.1080/07391102.2025.2483963

Mohammad Khalid, Mohammed H Alqarni, Ahmed I Foudah, Mishary Saad Al Oraby

{"title":"Reinventing PARP1 inhibition: harnessing virtual screening and molecular dynamics simulations to identify repurposed drugs for anticancer therapeutics.","authors":"Mohammad Khalid, Mohammed H Alqarni, Ahmed I Foudah, Mishary Saad Al Oraby","doi":"10.1080/07391102.2025.2483963","DOIUrl":"10.1080/07391102.2025.2483963","url":null,"abstract":"Poly (ADP-ribose) polymerase 1 (PARP1) is a nuclear protein that plays a pivotal role in DNA repair and has emerged as a promising target for cancer therapy. Repurposing existing FDA-approved drugs for PARP1 inhibition offers an accelerated route to drug discovery. Here, we present an integrated approach to drug repurposing for PARP1 inhibition while utilizing an integrated approach involving structure-based virtual screening and molecular dynamics (MD) simulations. First, a curated library of 3648 FDA-approved drugs from DrugBank was screened to identify potential candidates capable of binding to the PARP1. Our study reveals a subset of drug molecules with favorable binding profiles and stable interactions within the PARP1 active site. The standout candidate, Nilotinib, was selected based on its drug profile and subjected to a detailed analysis, including interaction studies and 500 ns all-atom MD simulations. By integrating multiple computational approaches, we provide a rational framework for the selection of Nilotinib, demonstrating its PARP1 binding features and potential for therapeutic development after further experimentation. This study highlights the power of computational methods in accelerating drug repurposing efforts, offering an efficient strategy for identifying novel therapeutic options for PARP1-associated diseases.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"7063-7074"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Designing of xanthine-based DPP-4 inhibitors: a structure-guided alignment dependent Multifacet 3D-QSAR modeling, and molecular dynamics simulation study. 基于黄嘌呤的 DPP-4 抑制剂的设计：结构引导配准依赖多方面 3D-QSAR 建模和分子动力学模拟研究。

IF 2.4 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-08-01 Epub Date: 2024-05-24 DOI: 10.1080/07391102.2024.2329787

Priya Bisht, Priyadarshi Gautam, Arka Bhattacharya, Rajveer Singh, Sant Kumar Verma

{"title":"Designing of xanthine-based DPP-4 inhibitors: a structure-guided alignment dependent Multifacet 3D-QSAR modeling, and molecular dynamics simulation study.","authors":"Priya Bisht, Priyadarshi Gautam, Arka Bhattacharya, Rajveer Singh, Sant Kumar Verma","doi":"10.1080/07391102.2024.2329787","DOIUrl":"10.1080/07391102.2024.2329787","url":null,"abstract":"The DPP-4 enzyme degrades incretin hormones GLP-1 and GIP. DPP-4 inhibitors are found effective in the prevention of the degradation of incretins. Xanthine scaffold-bearing molecules are reported as potential DPP-4 inhibitors for treating type 2 diabetes mellitus, e.g. the marketed drug linagliptin. In this work, structure-guided alignment-dependent atom- and Gaussian field-based 3D-QSAR have been performed on a dataset of 75 molecules. The robustness and predictive ability of the developed multifacet 3D-QSAR models were validated on different statistical parameters and found to be statistically fit. The favorable and unfavorable pharmacophoric features were mapped for each multifacet 3D-QSAR model based on three alignment sets (1-3). A five-point common pharmacophore hypothesis was generated separately for each set of alignments. The molecular dynamics simulations (up to 100 ns) were performed for the potent molecule from each alignment set (Compounds 12, 40 and 57) compared to reference standard linagliptin to study the binding energy and stability of target-ligand complexes. The MM-PBSA calculations revealed that the binding free energy and stability of compounds 12 (-40.324 ± 17.876 kJ/mol), 40 (-80.543 ± 21.782 kJ/mol) and 57 (-50.202 ± 16.055 kJ/mol) were better than the reference drug linagliptin (-20.390 ± 63.200 kJ/mol). The generated contour maps from structure-guided alignment-dependent multifacet 3D-QSAR models offer information about the structure-activity relationship (SAR) and ligand-target binding energy and stability data from MD simulation may be utilized to design and develop target selective xanthine-based novel DPP-4 inhibitors.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6971-6995"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unlocking therapeutic potential: computational insights into TREM2 protein targeting with FDA-approved drugs for neurodegeneration. 释放治疗潜力：通过计算深入了解 TREM2 蛋白靶向与 FDA 批准的神经变性药物的关系。

IF 2.4 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-08-01 Epub Date: 2024-02-19 DOI: 10.1080/07391102.2024.2317987

Mohammed Alrouji, Sabina Yasmin, Fahad A Alhumaydhi, Sharaf E Sharaf, Moyad Shahwan, Anas Shamsi

{"title":"Unlocking therapeutic potential: computational insights into TREM2 protein targeting with FDA-approved drugs for neurodegeneration.","authors":"Mohammed Alrouji, Sabina Yasmin, Fahad A Alhumaydhi, Sharaf E Sharaf, Moyad Shahwan, Anas Shamsi","doi":"10.1080/07391102.2024.2317987","DOIUrl":"10.1080/07391102.2024.2317987","url":null,"abstract":"Neurodegenerative diseases such as Alzheimer's disease (AD) pose a significant global health challenge that requires the exploration of innovative therapeutic strategies. Triggering receptor expressed on myeloid cells-2 (TREM2) is one of the critical proteins involved in immune regulation and neuroinflammation. It has emerged as a promising therapeutic target to develop treatments for neurodegenerative disorders like AD. Here, we employed a comprehensive virtual screening approach to identify potential small molecule inhibitors among FDA-approved drugs for TREM2. The docking study reveals significant binding affinity, ranging from -7.8 kcal/mol to -8.5 kcal/mol, for the elucidated hits against TREM2, accompanied by several crucial interactions. Among the repurposed drugs identified in the initial screening, Carpipramine, Clocapramine, and Pimozide stood out due to their notable binding potential and favorable drug profiling. Further, we conducted molecular dynamics (MD) simulations on the selected molecules that probed their structural dynamics and stability within the TREM2 binding pocket. The structural parameters and hydrogen bond dynamics remained remarkably stable throughout the simulated trajectories. Furthermore, we performed principal component analysis (PCA) and constructed free energy landscapes (FELs) to gain deeper insights into ligand binding and conformational flexibility of TREM2. The findings revealed that the elucidated molecules, Carpipramine, Clocapramine, and Pimozide, exhibited an exceptional fit within the binding pocket of TREM2 with remarkable stability and interaction patterns throughout the 500 ns simulation window. Interestingly, these molecules possessed a spectrum of anti-neurodegenerative properties and favorable drug profiles, which suggest their potential as promising drug candidates for repurposing in the treatment of AD.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6570-6580"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of glycation-induced concentration-dependent change in albumin structure and alteration in its binding capacity. 糖化引起的白蛋白结构浓度依赖性变化及其结合能力变化的影响。

IF 2.4 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-08-01 Epub Date: 2024-02-21 DOI: 10.1080/07391102.2024.2316783

Kailas Sonpasare, Dimple S Lalchandani, Laltanpuii Chenkual, Pavan Kumar Sathala, Raheema Khatoon, Pawan Kumar Porwal

{"title":"Effect of glycation-induced concentration-dependent change in albumin structure and alteration in its binding capacity.","authors":"Kailas Sonpasare, Dimple S Lalchandani, Laltanpuii Chenkual, Pavan Kumar Sathala, Raheema Khatoon, Pawan Kumar Porwal","doi":"10.1080/07391102.2024.2316783","DOIUrl":"10.1080/07391102.2024.2316783","url":null,"abstract":"Reducing sugars causes confirmatory alterations in albumin structure by the nonenzymatic glycation of the amino group of serum albumin. In this study, glucose and its hazardous metabolic products like glyoxal and methylglyoxal were incubated with bovine serum albumin (BSA). The confirmational changes in BSA molecule's structure by glycating substances was investigated using a variety of spectroscopic methods, including deconvolutionFourier Transform Infra-red (FT-IR) spectroscopy, fluorescence spectroscopy, UV spectroscopy and circular dichroism (CD) spectroscopy. Dynamic fluorescence quenching was observed in the case of glucose, while static quenching was observed in the case of methyl glyoxal and glyoxal. Similarly, employing deconvolution FT-IR spectroscopy and CD spectroscopy for determination of change in secondary structures in terms signature of α-helix, β-turn, β-sheet and random coil modifications. Destabilization or unfolding of the albumin structure, due to the disruption of the hydrogen bonding pattern that stabilizes the albumin manifold, causes a 25-50% reduction in α-helix and a 2-fold increase in β-sheet and turns in glycated BSA. The competitive displacement interaction studies with warfarin were performed using the ultrafiltration technique and quantitative determination of free drug in ultrafiltrate using LC-MS/MS. The binding of carbamazepine (CBZ) or its active metabolite to proteins was unaffected by the glycation of BSA with glucose and methyl glyoxal. Nevertheless, with glyoxal-modified BSA, it changed the binding of selected analytes significantly. Based on in vitro observations and results, it could be anticipated that the serum CBZ concentration variation may be worsened in uncontrolled diabetes circumstances, with an overall variance of 30-40% possible.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6488-6497"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0