Archives of biochemistry and biophysics最新文献

{"title":"Investigating the binding of fluorescent probes to a trypanosomal-tRNA synthetase: A fluorescence spectroscopic and molecular dynamics study.","authors":"Pratyasha Bhowal, David Jameson, Rajat Banerjee","doi":"10.1016/j.abb.2024.110263","DOIUrl":"10.1016/j.abb.2024.110263","url":null,"abstract":"<p><p>Given the high prevalence of Chagas disease in the Americas, we targeted the unique arginyl-tRNA synthetase of its causative agent Trypanosoma cruzi. Among their many possible uses, naphthalene-derived fluorescent ligands, such as ANS and bis-ANS, may be employed in pharmacokinetic research. Although ANS and bis-ANS have become prominent fluorescent probes for protein characterization, the structural and spectroscopic characteristics of protein-ANS/bis-ANS complexes remain largely unknown. Both fluorescent dyes bind to either the folded or partially folded hydrophobic regions of proteins. Additionally, they serve to identify molten globule-like intermediates. These probes have been used to study the folding problems of protein structures and the mechanisms of protein-protein interactions. ANS and bis-ANS exhibited significant enhancement and blue shift in their emission spectra upon binding to TcArgRS, the primary enzyme responsible for attaching l-arginine to its corresponding tRNA. Through fluorescence spectroscopy and computational studies, we concluded that bis-ANS binds more tightly to TcArgRS and that ATP affects bis-ANS fluorescence signal. Thus, these probes are useful resources for studying the intricate intermolecular relationships between proteins in terms of their structure, function, and mechanism. Our study provides a framework for identifying the hydrophobic regions present in TcArgRS. The utilization of hydrophobic patches on proteins for drug targeting is noteworthy because they can assist in identifying regions on the surface of proteins that are likely to interact with ligands. These patches help identify hotspot residues that play a vital role in determining binding affinity. Drugs are mainly small and hydrophobic in nature, and they target protein surfaces which have complementary properties. In this study, we elucidated the potential of TcArgRS as a target for combating trypanosomal diseases and extending life expectancy.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110263"},"PeriodicalIF":3.8,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805697","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}

{"title":"MXene-encapsulated ZIF-8@Liposomes for NIR-enhanced photothermal therapy in hepatocellular carcinoma treatment: In vitro, in vivo, and in silico study.","authors":"Shehab Elbeltagi, Nawal Madkhali, Hanan M Alharbi, Zienab E Eldin","doi":"10.1016/j.abb.2024.110256","DOIUrl":"10.1016/j.abb.2024.110256","url":null,"abstract":"<p><p>Photothermal therapy (PTT) utilizes near-infrared (NIR) light to enhance localized, non-invasive cancer treatments and drug delivery systems (DDS). Combination chemotherapy with PTT (chemo-PTT) offers multiple therapeutic advantages, involving synergistic effects, reduced side effects, and decreased drug toxicity. In this study, 2D titanium carbide (Ti₃C₂T_x) MXene nanosheets were encapsulated in a zeolitic imidazolate framework-8 (ZIF-8) to form (MX-ZIF-8) nanoparticles (NPs) for PTT applications. Sorafenib (SB), an anticancer drug was loaded onto MX-ZIF-8 and further modified with a liposomes (LPs) lipid bilayer to create (SB-MX-ZIF-8@LPs) nanocomposites. TEM imaging revealed that SB-MX-ZIF-8@LPs had a lamellar structure and spherical shape, with an average diameter of 75.2 nm and a zeta potential (ZP) of -8.4 ± 4.5 mV. Additionally, the PT stability, drug encapsulation, and in-vitro release kinetics of SB-MX-ZIF-8@LPs were assessed. These nanocomposites exhibited an impressive PT conversion efficiency of 55 % at 50 μg/mL under NIR irradiation. The cumulative release of SB from SB-MX-ZIF-8@LPs reached 86.15 % at pH 7.4 and 89.3 % at pH 4.8 under NIR over a period of 72 h, with an encapsulation efficiency of 87.34 %. MTT assays revealed strong cytotoxicity against HepG2 cells, with SB-MX-ZIF-8@LPs showing an IC₅₀ value of 2.7 μg/mL and inducing approximately 96 % total apoptosis. The SB-MX-ZIF-8@lip nanocomposite demonstrated excellent biological stability in a serum environment, retaining over 98 % of sorafenib and maintaining consistent particle size (∼347 nm) over 30 days. An in vivo xenograft study in BALB/c mice further demonstrated the efficacy of SB-MX-ZIF-8@LPs, with this treatment group showing the smallest tumor volume compared to other groups and a significantly higher tumor volume reduction than SB alone. Molecular docking studies indicated that SB exhibited strong binding affinities particularly with ABL1 (-8.7 kcal/mol) and EGFR (-9.3 kcal/mol). Docking interactions between MXene and SB, conducted using the Hdock Server, resulted in a docking score of -10.53, with one bond forming at a distance of 4 Å. These findings were consistent with experimental results, highlighting the favorable interaction between MXene and SB. ADMET analysis confirmed that MX-ZIF-8@LPs possessed favorable drug carrier properties, including high intestinal absorption (96.6 %), and low toxicity supporting its potential as an effective DDS for cancer therapy.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110256"},"PeriodicalIF":3.8,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783938","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}

{"title":"Differential effect of cerium nanoparticles on the viability, redox-status and Ca²⁺-signaling system of cancer cells of various origins.","authors":"Elena G Varlamova, Sergey V Gudkov, Egor A Turovsky","doi":"10.1016/j.abb.2024.110261","DOIUrl":"10.1016/j.abb.2024.110261","url":null,"abstract":"<p><p>The present study aims to understand the molecular mechanism underlying the therapeutic effect of cerium nanoparticles (CeNPs) in oncology. Cancer cells were treated with different concentrations of pure nanocerium of different sizes synthesized by laser ablation. Due to the not insignificant influence of surface defects and oxygen species on the ROS-modulating properties of cerium nanoparticles, the nanoparticles were not coated with surfactants or organic molecules during synthesis, which could potentially inhibit a number of pro-oxidative effects. Reactive oxygen species (ROS) production, expression of genes encoding redox-status proteins, selenoproteins and proteins regulating cell death and endoplasmic reticulum stress (ER-stress) were investigated as indicators of the molecular mechanism of cancer cell death. Studies were conducted on the effects of cerium nanoparticles on the Ca²⁺ signaling system of cancer cells of different origins. Mouse fibroblasts (L-929 cell line) were used as non-cancerous (\"normal\") cells for which a whole series of experiments were performed, and a comparative analysis of the effects of nanoceria. It was found that 75 nm-sized cerium nanoparticles did not affect the redox-status and ROS production of cancer cells. In fibroblast cells, however, this nanoparticle diameter led to a deterioration of the cellular redox status and ROS production in a wide range of nanoparticle concentrations. Larger nanoparticles (100 nm-sized and 160 nm-sized), on the other hand, showed a different effect on cancer cells of different origins. In mouse fibroblast L-929 cells, however, 100 nm-sized or 160 nm-sized CeNPs acted in a high concentration range to disrupt mitochondrial membrane potential and activate early apoptosis. High concentrations of CeNPs were required to increase ROS production, reduce redox-status and induce apoptosis in human A-172 glioblastoma cells compared to the hepatocellular carcinoma cell line HepG2 and the breast cancer cell line MCF-7. In the A-172 glioblastoma cells, ER-stress was also not activated and their Ca²⁺ signaling system was activated by a significantly higher concentration of CeNPs, which could also contribute to the formation of tolerance of this cancer cell line to nanoceria. The Ca²⁺ signaling system of mouse fibroblasts was found to be highly sensitive to activation by nanoceria and the cells produced Ca2+ signals with higher amplitude compared to A-172 and MCF-7 cells.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110261"},"PeriodicalIF":3.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790958","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}

{"title":"PROTAC-attractive site as a new target for suppressing P-glycoprotein activity.","authors":"Tatyana A Grigoreva, Aleksandra Sagaidak, Daria S Novikova, Vyacheslav G Tribulovich","doi":"10.1016/j.abb.2024.110258","DOIUrl":"10.1016/j.abb.2024.110258","url":null,"abstract":"<p><p>P-glycoprotein (P-gp) plays an important role in the rapid release of various small molecule substances from the cell. In turn, inhibition of this efflux transporter is an attractive strategy for both overcoming chemoresistance and facilitating oral absorption of drugs or CNS drug delivery. In this work, we adopt an approach typical for PROteolysis Targeting Chimera (PROTAC), which is based on the artificial drawing together of the target protein to E3 ubiquitin ligase, to P-gp. Forced ubiquitinylation of a transmembrane protein will provoke its removal from the cell membrane and promote its subsequent degradation. Within this concept, we investigated the possibility of P-gp ubiquitinylation by a number of PROTAC-specific E3 ligases using several approaches. We also identified the most promising site for the development of P-gp ligands. By screening a diversified library of compounds, we not only identified a number of scaffolds suitable for the construction of specific ligands, but also proposed dorsomorphin as a convenient platform for creating the constituent of a bifunctional chimera. We show that dorsomorphin both has the structural characteristics necessary to develop a PROTAC-like molecule and exhibits P-gp inhibitory activity. In conclusion, the proposed approach is universal and can be applied to other transmembrane proteins associated with the pathogenesis of certain diseases.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110258"},"PeriodicalIF":3.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783939","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}

{"title":"Retraction notice to “Role of sulfurous mineral water and sodium hydrosulfide as potent inhibitors of fibrosis in the heart of diabetic rats” [Archiv. Biochem. Biophys. 506 (2011) 48–57]","authors":"Mohamed M. El-Seweidy ,&nbsp;Nermin A.H. Sadik ,&nbsp;Olfat G. Shaker","doi":"10.1016/j.abb.2024.110174","DOIUrl":"10.1016/j.abb.2024.110174","url":null,"abstract":"","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"762 ","pages":"Article 110174"},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563883","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}

{"title":"Corrigendum to “Aldose reductase with quinolone antibiotics interaction: In vitro and in silico approach of its relationship with diabetic complications” [Arch. Biochem. Biophys. 761 (2024) 110161]","authors":"Cüneyt Türkeş","doi":"10.1016/j.abb.2024.110211","DOIUrl":"10.1016/j.abb.2024.110211","url":null,"abstract":"","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"762 ","pages":"Article 110211"},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613542","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}

{"title":"Tools to investigate oxygen-related challenges with flavin-dependent enzymes.","authors":"Ariadna Pié Porta, Elif Erdem, John M Woodley","doi":"10.1016/j.abb.2024.110246","DOIUrl":"10.1016/j.abb.2024.110246","url":null,"abstract":"<p><p>Enzymes have multiple applications in medicine but during the past decades interest in the application of enzymes as (bio)catalysts to produce a wide range of valuable molecules in various industries has increased. Many chemical compounds (from pharmaceuticals to bulk commodities) can be produced by a series of enzymatically-catalysed chemical steps, and in many cases one of these steps is an oxidation. The use of molecular oxygen as an oxidising agent in biocatalytic processes is a double-edged approach. From one side, the oxygen is supplied to the reactor in the form of air bubbling, which is cheap, highly available and non-toxic. From the other side, bubbling air into the reaction media creates a gas-liquid interface which adsorbs enzymes and compromises their stability. Moreover, the oxygen is quite insoluble in water, which often results in oxygen-limited reactions. These aspects are the main limiting factors for the stability and kinetics of enzymes that perform oxidative biocatalysis and prevent the reaction from happening at a rate that is high/competitive enough for industrial feasibility. Therefore, we need systems to mimic and understand better these factors to try and mitigate their effects upon scale-up. In this review, we present two complementary systems to study these factors: one apparatus that ensures a constant gas-liquid interface and another one that maintains a constant oxygen partial pressure. Both can provide highly valuable information regarding the maximum rate of reaction and about the deactivation profiles of enzymes in the presence of bubbles.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110246"},"PeriodicalIF":3.8,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765727","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}

{"title":"Catalytic insights of acetolactate synthases from different bacteria.","authors":"Yan-Fei Liang, Ze-Xin Niu, Zi-Wen Wu, Qing-Yang Zhang, Xin-Yi Zhao, Lei-Lei Chao, Heng Li, Wen-Yun Gao","doi":"10.1016/j.abb.2024.110248","DOIUrl":"10.1016/j.abb.2024.110248","url":null,"abstract":"<p><p>Acetolactate synthase (ALS) is an essential enzyme involved in the biosynthesis of platform chemicals acetoin and 2,3-butanediol in several microorganisms. In this study, we investigated the catalytic differences among three bacterial ALSs involved in the ligation of two molecules of pyruvate or 2-ketobutyrate. Based on the findings, we predicted three amino acid residues in each enzyme that caused a discrepancy in accordance with the multi-sequence alignment and molecular docking experiments: I398, A402, and T480 in Bacillus subtilis ALS; V400, Y404, and S482 in Listeria seleigeri serovar 1/2b ALS; and M394, H398, and G476 in Klebsiella pneumoniae ALS. Subsequently, we mutually mutated the residues in the three ALSs. The data obtained confirmed our inference that these three residues in each enzyme are truly correlated with substrate recognition, particularly in recognizing compounds that are larger than pyruvate, such as 2-ketobutyrate, benzaldehyde, and nitrosobenzene. This study further clarifies the biochemical traits of ALSs derived from various bacteria and expands the scope of ALS research.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110248"},"PeriodicalIF":3.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765719","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}

{"title":"The importance of helical structures to the overall activity and structural stability of a lipase from Pseudomonas aeruginosa PAO1 in n-hexane.","authors":"Jaidriel Meg G Cabanding, Steve S-F Yu, Zhi-Han Lin, Myrnel A Fortuna, Adam Jo J Elatico, Ricky B Nellas","doi":"10.1016/j.abb.2024.110226","DOIUrl":"10.1016/j.abb.2024.110226","url":null,"abstract":"<p><p>Bacterial lipases are versatile extracellular enzymes with a catalytic triad at the active site and a flexible 'lid' that modulates catalytic accessibility. We combined computational modeling with preliminary in vitro testing to assess the structural stability and activity of the Pseudomonas aeruginosa PAO1 lipase (PAL). We evaluated several systems consisting of the native and mutant forms of the lipase in n-hexane using molecular dynamics simulations. Structural stability was assessed by calculating the B-factor for each system. We measured the gorge radius of the catalytic channel and the RMSD of the catalytic triad to approximate enzymatic activity. Based on the correlation of these metrics, mutant forms were selected for their potential activity and stability. Selected mutant forms were expressed in E. coli BL21, mass-produced, and validated through a lipase-catalyzed esterification assay in n-hexane. Several helices outside the 'lid' region were found to influence lid conformational switching. Moreover, our preliminary experimental results show promise in validating our in silico predictions. Our integrated in silico and in vitro pipeline offers a promising approach for designing and producing industrially relevant lipases.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110226"},"PeriodicalIF":3.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765724","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}

{"title":"New metal complexes of 1H-benzimidazole-2-yl hydrazones: Cytostatic, proapoptotic and modulatory activity on kinase signaling pathways.","authors":"Maria Argirova, Emiliya Cherneva, Rositsa Mihaylova, Georgi Momekov, Denitsa Yancheva","doi":"10.1016/j.abb.2024.110245","DOIUrl":"10.1016/j.abb.2024.110245","url":null,"abstract":"<p><p>The copper complexes of two 1H-benzimidazole-2-yl hydrazones were obtained by complexation with copper chloride. The molecular structure of the complexes was studied by microchemical analysis, SEM-EDX, IR and micro-Raman spectroscopy and DFT calculations. It was found that both ligands form 1:1 complexes with the copper, where the Cu ions are coordinated by N-atom from the benzimidazole ring, N-atom of the azomethine bond, O-atom from the ortho-OH group of the aromatic ring and one chlorine atom. The coordination process significantly affected their cytotoxicity profile. The conversion of 2-(2-hydroxybenzylidene)-1-(1H-benzimidazol-2-yl)hydrazine 1.1. into a Cu complex 2.1. led to a 2.4-fold increase in its antileukemic activity against AR-230 cells and an 8-fold increase in the cytostatic activity against MCF-7 breast cancer cell line. The growth-inhibitory effect of the Cu complex of 2-(2-hydroxy-4-methoxybenzylidene)-1-(1H-benzimidazol-2-yl)hydrazine 2.2. on the MCF-7 cells was comparable to that of the respective ligand, however lacked towards the leukemic AR-230 cell population. Regarding their cytotoxic potential towards CCL-1 cells, both Cu complexes exhibited a weaker selectivity pattern as compared to their ligands. The proapoptotic and modulatory activity of 1.1 and 2.1. on key kinase signaling pathways was further studied in the ER + breast cancer (MCF-7) and bcr-abl + leukemic (AR-230) in vitro tumor models in a comparative manner to the reference drugs tamoxifen and imatinib, respectively. Inhibition of the JAK/STAT signaling pathway was outlined as a prominent mechanism in the antileukemic activity against the Ph + AR-230 in vitro model, whereas recruitment and activation of the extrinsic apoptotic pathway was established in the MCF-7 cells.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110245"},"PeriodicalIF":3.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765720","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}