Biochimie最新文献_第7页

Crystal structure of Leishmania orientalis triosephosphate isomerase at 1.88 Å resolution and its specific inhibitors 1.88 Å分辨率下东方利什曼原虫三磷酸异构酶的晶体结构及其特异性抑制剂。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-19 DOI: 10.1016/j.biochi.2025.02.004

Buabarn Kuaprasert , Ubolsree Leartsakulpanich , Pinpunya Riangrungroj , Wichai Pornthanakasem , Wipa Suginta , Mathirut Mungthin , Saovanee Leelayoova , Duangnapa Kiriwan , Kiattawee Choowongkomon

{"title":"Crystal structure of Leishmania orientalis triosephosphate isomerase at 1.88 Å resolution and its specific inhibitors","authors":"Buabarn Kuaprasert , Ubolsree Leartsakulpanich , Pinpunya Riangrungroj , Wichai Pornthanakasem , Wipa Suginta , Mathirut Mungthin , Saovanee Leelayoova , Duangnapa Kiriwan , Kiattawee Choowongkomon","doi":"10.1016/j.biochi.2025.02.004","DOIUrl":"10.1016/j.biochi.2025.02.004","url":null,"abstract":"<div><div><em>Leishmania orientalis</em>, previously called <em>L. siamensis</em>, is a new species characterized as causing cutaneous leishmaniasis in Thailand. This study solves the crystal structure of the <em>L. orientalis</em> triosephosphate isomerase (<em>Lo</em>TIM) in apo form at 1.88 Å resolution by using molecular replacement method. Tyrosine118 presents in the LoTIM protein sequence, whereas <em>L. mexicana</em> and <em>Trypanosoma cruzi</em> TIMs have a relative Cys118, which plays a major role in their specific ligand binding. Sulfur atom of the Cys57 thiol group is covalently bound to an arsenic (As) atom present in the precipitating solution. Although the electron density of loop-6 (Gly174-Tyr175-Gly176-Lys177-Val178) is missing in the structure due to this region lacking rigidity, the biological assembly of the two monomers of the <em>Lo</em>TIM crystal structures are like that of <em>L. mexicana</em> and <em>T. cruzi</em>. 3D molecular protein-ligand docking was performed using the dimeric interfacial pocket of the enzyme as a ligand-binding receptor to identify its specific inhibitors. Five potential inhibiting compounds, including NSC639174, NSC606498, NSC110039, NSC58446, and NSC345647, were obtained with their <em>IC</em><sub>50</sub> 2.79 ± 0.10, 3.28 ± 0.80, 3.67 ± 0.11, 4.59 ± 0.87 and 15.44 ± 0.14 μM, respectively. However, specific inhibition assays against TIMs from <em>L. orientalis</em> and rabbit muscle indicate that NSC639174 and NSC110039 are the most potent inhibitors for <em>Lo</em>TIM, whereas NSC58446 inhibits well both the parasitic and rabbit enzymes.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"233 ","pages":"Pages 27-35"},"PeriodicalIF":3.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473266","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

The prolyl oligopeptidase and α-synuclein connection revisited 重新审视脯氨酸寡肽酶和α-突触核蛋白的联系。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-19 DOI: 10.1016/j.biochi.2025.02.003

Roos Van Elzen , Yannick Waumans , Sangeeta Nath , Pieter Van der Veken , Sonja Kerkhoff , Evert Van Dijk , Markus Morawski , Steffen Roßner , Yves Engelborghs , Ingrid De Meester , Anne-Marie Lambeir

{"title":"The prolyl oligopeptidase and α-synuclein connection revisited","authors":"Roos Van Elzen , Yannick Waumans , Sangeeta Nath , Pieter Van der Veken , Sonja Kerkhoff , Evert Van Dijk , Markus Morawski , Steffen Roßner , Yves Engelborghs , Ingrid De Meester , Anne-Marie Lambeir","doi":"10.1016/j.biochi.2025.02.003","DOIUrl":"10.1016/j.biochi.2025.02.003","url":null,"abstract":"<div><div>The aim of this work was to revisit the connection between prolyl oligopeptidase (PREP) and α-synuclein (aSyn) by presenting novel data from cell free and cellular assays and to discuss the results in a contemporary context.</div><div>The aSyn aggregation process was studied using fluorescence correlation spectroscopy and thioflavin-T fluorescence. Binding sites for PREP on the aSyn sequence were determined using peptide arrays. Subcellular localisation of PREP and stress markers were studied using double staining immunofluorescence microscopy in SH-SY5Y cells with and without overexpression of aSyn and PREP, before and after differentiation, and with or without proteolytic stress induced by proteasome inhibition.</div><div>The interaction between PREP and aSyn was found to be weak and transient. It promotes the early phases of aggregation but does not affect the rate of β-fibril formation. Moreover, this interaction is not dependent upon the C-terminal prolines of aSyn, but is affected by PREP inhibitors and interferes with PREP substrate binding. Although present in the same cellular compartments, there is little evidence for a strong physical association of PREP with aggresomes and stress markers. Instead, there is colocalization with aSyn in the cell periphery and neurites.</div><div>There is evidence for a binding site for peptides much longer than the usual PREP substrates. The modular assembly of molecular machines and the observation that PREP's protein-protein interactions are tuneable by active site inhibitors, lead to the hypothesis that this binding site features in the cross-talk between autophagy and neuron-specific pathways involving vesicle transport and protein secretion.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"233 ","pages":"Pages 1-13"},"PeriodicalIF":3.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473206","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

Editor's Note to '27-hydroxycholesterol decreases cell proliferation in colon cancer cell lines' [Biochimie 153 (2018) 171-180] 编者按。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-06 DOI: 10.1016/j.biochi.2025.02.001

引用次数: 0

Fluor NMR study of amino acid derived ligand to study TSPO 氨基酸衍生配体的荧光核磁共振研究TSPO。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-04 DOI: 10.1016/j.biochi.2025.01.015

Luminita Duma , Severine Schneider , Agathe Martinez , Cathy Hachet , Frederic Bihel , Jean-Jacques Lacapere

{"title":"Fluor NMR study of amino acid derived ligand to study TSPO","authors":"Luminita Duma , Severine Schneider , Agathe Martinez , Cathy Hachet , Frederic Bihel , Jean-Jacques Lacapere","doi":"10.1016/j.biochi.2025.01.015","DOIUrl":"10.1016/j.biochi.2025.01.015","url":null,"abstract":"<div><div>Translocator protein (TSPO, 18 kDa), previously known as peripheral-type benzodiazepine receptor, is an evolutionarily conserved membrane protein involved in various physiological processes and patho-physiological conditions. The endogeneous TSPO ligand is a polypeptide of 9 kDa, but dipeptides with biological activity have been previously synthesized and characterized. Herein, we synthesized a phenyl alanine derived ligand with a <sup>19</sup>F labelling which opens prospective for <sup>19</sup>F-MRI and potential <sup>18</sup>F-PET applications. We characterized the coexistence of two conformers that are not equally sensitive to the media used for membrane protein studies. Interaction studies with the recombinant mouse TSPO (mTSPO) in different membrane-mimicking environments are presented using <sup>19</sup>F NMR enabling structure/function characterizations. A change in the mTSPO environment from pure detergent to lipid/detergent mixture reveals different exchange rates between bound and free ligand forms. Competition experiments with the high-affinity drug ligand (<em>R</em>)-PK 11195 suggests that phenyl alanine derived ligand binds in the same protein cavity.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"233 ","pages":"Pages 14-26"},"PeriodicalIF":3.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolic adaptation mechanisms of glycogen reduction and lipid accumulation in testicular protection in Daurian ground squirrels during hibernation 达斡尔地松鼠冬眠期间睾丸保护中糖原减少和脂质积累的代谢适应机制。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-03 DOI: 10.1016/j.biochi.2025.01.014

Ming-Di Wang , Lu-Fan Li , Yu-Jing Yan , Xing-Chen Wang , Le Chen , Kai Dang , Zhe Wang , Hui-Ping Wang

{"title":"Metabolic adaptation mechanisms of glycogen reduction and lipid accumulation in testicular protection in Daurian ground squirrels during hibernation","authors":"Ming-Di Wang , Lu-Fan Li , Yu-Jing Yan , Xing-Chen Wang , Le Chen , Kai Dang , Zhe Wang , Hui-Ping Wang","doi":"10.1016/j.biochi.2025.01.014","DOIUrl":"10.1016/j.biochi.2025.01.014","url":null,"abstract":"<div><div>The role of glycogen and lipid metabolism in the testes of Daurian ground squirrels (<em>Spermophilus dauricus</em>) during different stages of the hibernation cycle and their influence on reproductive function remain poorly understood. This study examined testicular morphology across hibernation stages and investigated potential molecular mechanisms. Results showed that: (1) Spermatocyte density was reduced in the torpor group compared to the pre-hibernation (PRE) group, suggesting a suppression of spermatogenesis during torpor. In the post-hibernation (POST) group, reduced spermatocyte density was speculated to correspond to the initial phase of spermatocyte maturation into spermatozoa. (2) Glycogen content was lower during interbout arousal (IBA), while glycogen phosphorylase (GP) activity was significantly elevated compared to the other stages. Sertoli cell density was higher in the IBA group relative to the torpor group, suggesting that elevated GP activity facilitates glycogen breakdown, providing glycolytic substrates for Sertoli cells during this phase. (3) During torpor, triglyceride and fatty acid levels, along with fatty acid synthase and acetyl-CoA carboxylase activities, remained consistent with PRE levels. These findings suggest that fatty acids are crucial for maintaining testicular reproductive function during torpor. In contrast, lipid metabolism indicators declined during the near post-hibernation (NP) and POST stages, likely supporting the rapid reactivation of reproductive processes required for the upcoming breeding season. In summary, this study highlights a dynamic interplay between lipid and glycogen metabolism across hibernation stages, with the transition from lipid-based metabolism during torpor to glycogen utilization during IBA playing a pivotal role in sustaining testicular homeostasis in Daurian ground squirrels.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"232 ","pages":"Pages 133-141"},"PeriodicalIF":3.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256160","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

Engineered IgG Fc-conjugation prolongs the half-life of florfenicol and alleviates pneumonia in mice 经改造的 IgG Fc 连接可延长氟苯尼考的半衰期并缓解小鼠肺炎。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.10.014

Shikun Ge , Mei Dang , Alberto Carlos Pires Dias , Xiaoying Zhang

引用次数: 0

Analysis of the relationship between resistin with prognosis, cell migration, and p38 and ERK1/2 activation in breast cancer 电阻素与乳腺癌预后、细胞迁移以及 p38 和 ERK1/2 激活之间的关系分析。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.10.001

Reyna L. Cuachirria-Espinoza , Alin García-Miranda , Rafael Hernández-Barragán, Dania A. Nava-Tapia, Monserrat Olea-Flores, Napoleón Navarro-Tito

{"title":"Analysis of the relationship between resistin with prognosis, cell migration, and p38 and ERK1/2 activation in breast cancer","authors":"Reyna L. Cuachirria-Espinoza , Alin García-Miranda , Rafael Hernández-Barragán, Dania A. Nava-Tapia, Monserrat Olea-Flores, Napoleón Navarro-Tito","doi":"10.1016/j.biochi.2024.10.001","DOIUrl":"10.1016/j.biochi.2024.10.001","url":null,"abstract":"<div><div>Obesity increases the risk and mortality of breast cancer through dysregulated secretion of proinflammatory cytokines and tumor adipokines that induce an inflammatory breast microenvironment. Resistin is an adipokine secreted by adipocytes, immune cells, and predominantly macrophages, which contributes to cancer progression, but its molecular mechanism in cancer is not completely described. In this study, we analyzed the relationship of resistin on breast cancer prognosis and tumor progression and the effect <em>in vitro</em> of resistin on p38 and ERK1/2 activation in breast cancer cell lines. By bioinformatic analysis, we found that resistin is overexpressed in the basal subtype triple-negative breast cancer and is related to poor prognosis. In addition, we demonstrated a positive correlation between <em>RETN</em> and <em>MAPK3</em> expression in basal triple-negative breast cancer. Importantly, we found amplifications of the <em>RETN</em> gene in at least 20 % of metastatic samples from patients with breast cancer. Most samples with <em>RETN</em> amplifications metastasized to bone and showed high expression of IL-8 (<em>CXCL8</em>) and IL-6 (<em>IL6</em>). Finally, resistin could be considered a prognostic marker for basal triple-negative breast cancer, and we also proposed the possibility that resistin-induced cell migration involves the activation of MAPK in breast cancer cells.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 19-29"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382734","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

Structural extracellular matrix-mediated molecular signaling in wound repair and tissue regeneration 细胞外基质结构介导的分子信号在伤口修复和组织再生中的作用。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.10.003

Sousan Cheong , Yujie Peng , Feng Lu, Yunfan He

{"title":"Structural extracellular matrix-mediated molecular signaling in wound repair and tissue regeneration","authors":"Sousan Cheong , Yujie Peng , Feng Lu, Yunfan He","doi":"10.1016/j.biochi.2024.10.003","DOIUrl":"10.1016/j.biochi.2024.10.003","url":null,"abstract":"<div><div>The extracellular matrix (ECM) is a complex, non-cellular network of molecules that offers structural support for cells and tissues. The ECM is composed of various structural components, including collagen, fibronectin, laminin, perlecan, nidogen, tenascin, and fibulin, which are capable of binding to each other and to cell-to-adhesion receptors, endowing the ECM with unique physical and biochemical properties that are essential for its function in maintaining health and managing disease. Over the past three decades, extensive research has shown that the core of the ECM can significantly impact cellular events at the molecular level. Structural modifications have also been strongly associated with tissue repair. Through interactions with cells, matrix proteins regulate critical processes such as cell proliferation and differentiation, migration, and apoptosis, essential for maintaining tissue homeostasis, formation, and regeneration. This review emphasizes the interlocking networks of ECM macromolecules and their primary roles in tissue regeneration and wound repair. Through studying ECM dynamics, researchers have discovered molecular signaling pathways that demonstrate how the ECM influences protein patterns and open up more possibilities for developing therapeutics that target the ECM to enhance wound repair and tissue regeneration.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 58-68"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382736","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

Daphnetin weakened the pathogenicity of methicillin-resistant Staphylococcus aureus by inhibiting Sortase A and α-hemolysin Daphnetin 可抑制 Sortase A 和 α 溶血素，从而削弱耐甲氧西林金黄色葡萄球菌的致病性。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.10.010

Shuyue Zhu , Chunjie Hu , Yan Wang , Mengli Jin , Qiuyue Zhang , Shaoyu Han , Yating Tang , Desheng Wu , Di Fu , Shuang Jiang , Danning Song , Lin Wei , Wu Song , Chi Zhang , Wenfeng Zhang

{"title":"Daphnetin weakened the pathogenicity of methicillin-resistant Staphylococcus aureus by inhibiting Sortase A and α-hemolysin","authors":"Shuyue Zhu , Chunjie Hu , Yan Wang , Mengli Jin , Qiuyue Zhang , Shaoyu Han , Yating Tang , Desheng Wu , Di Fu , Shuang Jiang , Danning Song , Lin Wei , Wu Song , Chi Zhang , Wenfeng Zhang","doi":"10.1016/j.biochi.2024.10.010","DOIUrl":"10.1016/j.biochi.2024.10.010","url":null,"abstract":"<div><div>The increasing prevalence of antibiotic-resistant bacteria, represented by Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA), has necessitated a shift towards anti-virulence strategies in treatment approaches. This research demonstrated that daphnetin effectively disrupted MRSA virulence by targeting Sortase A (SrtA), an enzyme in <em>Staphylococcus aureus</em> (<em>S. aureus</em>) responsible for adhesion and invasion, as well as the toxin <em>α</em>-hemolysin (Hla) that leads to cell lysis. Utilizing Fluorescence Resonance Energy Transfer, daphnetin showed direct inhibitory effect on SrtA activity, with an IC<sub>50</sub> of 25.98 μg/mL. Additionally, daphnetin hindered various SrtA-mediated processes in <em>S. aureus</em>, such as fibronectin adherence, A549 cell invasion, biofilm formation, and bacterial motility. Daphnetin inhibited <em>S. aureus</em>-induced hemolysis and reduced Hla expression as confirmed by Western blot analysis. Molecular docking studies identified specific binding sites of daphnetin with SrtA, highlighting key amino acid residues like GLU-77, TYR-75, and LYS-145, with a docking score of −7.139 kcal/mol. Besides that, daphnetin exhibited a protective effect on MRSA-induced pneumonia <em>in vivo</em>. In summary, daphnetin, a natural compound, effectively inhibited SrtA and Hla activities, attenuating MRSA virulence and showcasing potential for treating bacterial infections.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 84-94"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482917","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

Enzymatic tools for mitochondrial genome manipulation 线粒体基因组操作的酶工具。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.10.013

Beatrisa Rimskaya , Nikita Shebanov , Nina Entelis , Ilya Mazunin

{"title":"Enzymatic tools for mitochondrial genome manipulation","authors":"Beatrisa Rimskaya , Nikita Shebanov , Nina Entelis , Ilya Mazunin","doi":"10.1016/j.biochi.2024.10.013","DOIUrl":"10.1016/j.biochi.2024.10.013","url":null,"abstract":"<div><div>Mutations in mitochondrial DNA (mtDNA) can manifest phenotypically as a wide range of neuromuscular and neurodegenerative pathologies that are currently only managed symptomatically without addressing the root cause. A promising approach is the development of molecular tools aimed at mtDNA cutting or editing. Unlike nuclear DNA, a cell can have hundreds or even thousands of mitochondrial genomes, and mutations can be present either in all of them or only in a subset. Consequently, the developed tools are aimed at reducing the number of copies of mutant mtDNA or editing mutant nucleotides. Despite some progress in the field of mitochondrial genome editing in human cells, working with model animals is still limited due to the complexity of their creation. Furthermore, not all existing editing systems can be easily adapted to function within mitochondria. In this review, we evaluate the mtDNA editing tools available today, with a particular focus on specific mtDNA mutations linked to hereditary mitochondrial diseases, aiming to provide an in-depth understanding of both the opportunities and hurdles to the development of mitochondrial genome editing technologies.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 114-128"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482919","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