Biochimie最新文献_第2页

Complete analysis of G-quadruplex forming sequences in the gapless assembly of human chromosome Y 人类 Y 染色体无间隙组装中 G-四叠体形成序列的完整分析。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.10.007

Michaela Dobrovolná , Jean-Louis Mergny , Václav Brázda

{"title":"Complete analysis of G-quadruplex forming sequences in the gapless assembly of human chromosome Y","authors":"Michaela Dobrovolná , Jean-Louis Mergny , Václav Brázda","doi":"10.1016/j.biochi.2024.10.007","DOIUrl":"10.1016/j.biochi.2024.10.007","url":null,"abstract":"<div><div>Recent advancements have finally delivered a complete human genome assembly, including the elusive Y chromosome. This accomplishment closes a significant knowledge gap. Prior efforts were hampered by challenges in sequencing repetitive DNA structures such as direct and inverted repeats. We used the G4Hunter algorithm to analyze the presence of G-quadruplex forming sequences (G4s) within the current human reference genome (GRCh38) and the new telomere-to-telomere (T2T) Y chromosome assemblies. This analysis served a dual purpose: identifying the location of potential G4s within the genomes and exploring their association with functionally annotated sequences. Compared to GRCh38, the T2T assembly exhibited a significantly higher prevalence of G-quadruplex forming sequences. Notably, these repeats were abundantly located around precursor RNA, exons, genes, and within protein binding sites. This remarkable co-occurrence of G4-forming sequences with these critical regulatory regions suggests their role in fundamental DNA regulation processes. Our findings indicate that the current human reference genome significantly underestimated the number of G4s, potentially overlooking their functional importance.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 49-57"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402319","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

Central nervous system pathways targeted by amylin in the regulation of food intake 淀粉样蛋白调节食物摄入量的中枢神经系统途径。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.10.012

Mohammed K. Hankir , Christelle Le Foll

{"title":"Central nervous system pathways targeted by amylin in the regulation of food intake","authors":"Mohammed K. Hankir , Christelle Le Foll","doi":"10.1016/j.biochi.2024.10.012","DOIUrl":"10.1016/j.biochi.2024.10.012","url":null,"abstract":"<div><div>Amylin is a peptide hormone co-released with insulin from pancreatic β-cells during a meal and primarily serves to promote satiation. While the caudal hindbrain was originally implicated as a major site of action in this regard, it is becoming increasingly clear that amylin recruits numerous central nervous system pathways to exert multifaceted effects on food intake. In this Review, we discuss the evidence derived from preclinical studies showing that amylin and the related peptide salmon calcitonin (sCT) directly or indirectly target genetically distinct neurons in the caudal hindbrain (nucleus tractus solitarius and area postrema), rostral hindbrain (lateral parabrachial nucleus), midbrain (lateral dorsal tegmentum and ventral tegmental area) and hypothalamus (arcuate nucleus and parasubthalamic nucleus) via activation of amylin and/or calcitonin receptors. Given that the stable amylin analogue cagrilintide is under clinical development for the treatment of obesity, it is important to determine whether this drug recruits overlapping or distinct central nervous system pathways to that of amylin and sCT with implications for minimising any aversive effects it potentially causes. Such insight will also be important to understand how amylin and sCT analogues synergize with other molecules as part of dual or triple agonist therapies for obesity, especially the glucagon-like peptide 1 receptor (GLP-1R) agonist semaglutide, which has been shown to synergistically lower body weight with cagrilintide (CagriSema) in clinical trials.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 95-104"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482916","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

Human anti-apoptotic Bcl-2 and Bcl-xL proteins protect yeast cells from aging induced oxidative stress 人类抗凋亡蛋白 Bcl-2 和 Bcl-xL 保护酵母细胞免受老化诱导的氧化应激。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.10.009

Ayşenur Güler , Berna Kavakcıoğlu Yardımcı , Nihal Şimşek Özek

{"title":"Human anti-apoptotic Bcl-2 and Bcl-xL proteins protect yeast cells from aging induced oxidative stress","authors":"Ayşenur Güler , Berna Kavakcıoğlu Yardımcı , Nihal Şimşek Özek","doi":"10.1016/j.biochi.2024.10.009","DOIUrl":"10.1016/j.biochi.2024.10.009","url":null,"abstract":"<div><div>Aging is a degenerative, biological, and time-dependent process that affects all organisms. Yeast aging is a physiological phenomenon characterized by the progressive transformation of yeast cells, resulting in modifications to their viability and vitality. Aging in yeast cells is comparable to that in higher organisms in some respects; however, due to their straightforward and well-characterized genetic makeup, these cells present unique advantages when it comes to researching the aging process. Here, we assessed the impact of human anti-apoptotic Bcl-2 and Bcl-xL proteins on aging using a yeast model. The findings clearly showed that these proteins exhibited remarkable anti-aging properties in yeast cells. Our data indicate that the presence of both proteins enhanced the reproductive survival of aging cells, likely by effecting the components functioning as both pro- and anti-oxidants, depending on the stage of yeast cell lifespan. Both proteins partially protected yeast cells from aging-related morphological deformations and cellular damage during the aging period. In particular, Bcl-xL expressing yeast cells reached the maximum activity levels for almost all of the major antioxidant enzymes and the total antioxidant status on the 8th day of lifespan and could provide effective protection at the latest stage of the investigated aging period. The chemometric data analysis of IR spectra confirmed the findings of the morphological and biochemical analyses. In this regard, specifically, understanding the mechanism of action on the cellular redox state of Bcl-xL in yeast may facilitate comprehension of its indirect antioxidant function in higher eukaryotes.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 69-83"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482920","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}

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Inside front cover-EDB

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-01 DOI: 10.1016/S0300-9084(25)00003-3

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Site-directed mutagenesis of nattokinase: Unveiling structure-function relationship for enhanced functionality 纳豆激酶的定点突变：揭示结构-功能关系以增强功能

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.09.014

Ankush Jain, Pradeep Kumar Anand, Jagdeep Kaur

{"title":"Site-directed mutagenesis of nattokinase: Unveiling structure-function relationship for enhanced functionality","authors":"Ankush Jain, Pradeep Kumar Anand, Jagdeep Kaur","doi":"10.1016/j.biochi.2024.09.014","DOIUrl":"10.1016/j.biochi.2024.09.014","url":null,"abstract":"<div><div>Site-directed mutagenesis was employed to investigate the structure-function relationship of nattokinase (NK) and its effect on the enzymatic activity, thermostability, pH tolerance, and fibrinolytic properties of NK. Specific mutations (T270S, V271I, E262D, and A259T) were introduced within the nk gene, targeting regions predicted to be involved in substrate binding. The NK(E262D) mutant exhibited a significant increase in enzymatic activity (2-fold) and catalytic efficiency (2.2-fold) as assessed by N-Succinyl-Ala-Ala-Pro-Phe p-nitroanilide (Suc-AAPF-pNA) hydrolysis, compared to the wild type. <em>In silico</em> analysis supported these findings, demonstrating lower binding energy for the NK(E262D) mutant, suggesting stronger fibrin affinity. Thermostability assays revealed that NK(E262D) and NK(A259T) displayed exceptional stability, retaining enzyme activity at 60 °C. All mutants exhibited a broader pH tolerance range (pH 5.0–10.0) compared to the wild-type NK. The fibrinolytic activity assay revealed that the E262D mutant possessed the highest fibrinolytic activity (2414 U/mg), surpassing the wild-type. This study reported an NK variant with improved enzymatic activity, thermostability, and fibrinolytic properties.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 1-8"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334288","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

Robust approach for production of the human oncology target Aurora kinase B in complex with its binding partner INCENP 生产人类肿瘤靶标极光激酶 b 与其结合伙伴 incenp 复合物的稳健方法。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.10.011

Jonna Mattsson , Per Rogne , Maréne Landström , Magnus Wolf-Watz

{"title":"Robust approach for production of the human oncology target Aurora kinase B in complex with its binding partner INCENP","authors":"Jonna Mattsson , Per Rogne , Maréne Landström , Magnus Wolf-Watz","doi":"10.1016/j.biochi.2024.10.011","DOIUrl":"10.1016/j.biochi.2024.10.011","url":null,"abstract":"<div><div>Protein kinases are key players in many eukaryotic signal transduction cascades and are as a result often linked to human disease. In humans, the mitotic protein kinase family of Aurora kinases consist of three members: Aurora A, B and C. All three members are involved in cell division with proposed implications in various human cancers. The human Aurora kinase B has in particular proven challenging to study with structural biology approaches, and this is mainly due to difficulties in producing the large quantities of active enzyme required for such studies. Here, we present a novel and <em>E. coli</em>-based production system that allows for production of milligram quantities of well-folded and active human Aurora B in complex with its binding partner INCENP. The complex is produced as a continuous polypeptide chain and the resulting fusion protein is cleaved with TEV protease to generate a stable and native heterodimer of the Aurora B:INCENP complex. The activity, stability and degree of phosphorylation of the protein complex was quantified by using a coupled ATPase assay, <sup>31</sup>P NMR spectroscopy and mass spectrometry. The developed production system enables isotope labeling and we here report the first <sup>1</sup>H–<sup>15</sup>N-HSQC of the human Aurora B:INCENP complex. Our developed production strategy paves the way for future structural and functional studies of Aurora B and can as such assist the development of novel anticancer drugs targeting this important mitotic protein kinase.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 129-140"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482922","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

The effect of extremolytes ectoine and hydroxyectoine on the heat-induced protein aggregation: The case of growth hormone 极性溶解物埃克托因和羟基埃克托因对热诱导蛋白质聚集的影响：以生长激素为例

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.10.006

Rūta Gruškienė, Jolanta Sereikaitė

{"title":"The effect of extremolytes ectoine and hydroxyectoine on the heat-induced protein aggregation: The case of growth hormone","authors":"Rūta Gruškienė, Jolanta Sereikaitė","doi":"10.1016/j.biochi.2024.10.006","DOIUrl":"10.1016/j.biochi.2024.10.006","url":null,"abstract":"<div><div>The extremolytes ectoine and hydroxyectoine are osmolytes found in extremophilic microorganisms. They are stabilisers of proteins and other macromolecules, including DNA and lipids. The aim of the study was to investigate the effect of the additives on the heat-induced aggregation of mink growth hormone as a model protein. The first-order rate constants of protein aggregation were determined at 60 °C depending on the additive concentration and pH of the solution. The onset temperature of aggregation was also recorded using a circular dichroism spectropolarimeter. The study showed that the effect of the additives depended on the pH of the solution. The first-order rate constants of aggregation were lower when the protein molecule had a negative charge. The effect also depended on the structure of the extremolyte itself. When the protein molecule was positively charged, hydroxyectoine destabilised the mink growth hormone molecule and promoted the aggregation. The different effects of the additives were determined by the different interactions with the protein molecules, as shown by circular dichroism measurements and previously by fluorescence spectroscopy. Therefore, when using ectoine or hydroxyectoine for protein formulation, the effect of the additive should be carefully analysed for each protein individually.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 42-48"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402320","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

Mitochondrial dynamics: Molecular mechanism and implications in endometriosis

IF 3.3 3区生物学

Biochimie Pub Date : 2025-01-28 DOI: 10.1016/j.biochi.2025.01.012

Ylenia Marino , Francesca Inferrera , Tiziana Genovese , Salvatore Cuzzocrea , Roberta Fusco , Rosanna Di Paola

{"title":"Mitochondrial dynamics: Molecular mechanism and implications in endometriosis","authors":"Ylenia Marino , Francesca Inferrera , Tiziana Genovese , Salvatore Cuzzocrea , Roberta Fusco , Rosanna Di Paola","doi":"10.1016/j.biochi.2025.01.012","DOIUrl":"10.1016/j.biochi.2025.01.012","url":null,"abstract":"<div><div>Endometriosis affects about 10 % of women of reproductive age, leading to a disabling gynecologic condition. Chronic pain, inflammation, and oxidative stress have been identified as the molecular pathways involved in the progression of this disease, although its precise etiology remains uncertain. Although mitochondria are considered crucial organelles for cellular activity, their dysfunction has been linked to the development of this disease. The purpose of this review is to examine the functioning of the mitochondrion in endometriosis: in particular, we focused on the mitochondrial dynamics of biogenesis, fusion, and fission. Since excessive mitochondrial activity is reported to affect cell proliferation, we also considered mitophagy as a mechanism involved in limiting disease development. To better understand mitochondrial activity, we also considered alterations in circadian rhythms, the gut microbiome, and estrogen receptors: indeed, these mechanisms are also involved in the development of endometriosis. In addition, we focused on recent research about the impact of numerous substances on mitochondrial activity; some of them may offer a future breakthrough in endometriosis treatment by acting on mitochondria and inhibiting cell proliferation.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"231 ","pages":"Pages 163-175"},"PeriodicalIF":3.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069972","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

Structure and function analysis of microcystin transport protein MlrD

IF 3.3 3区生物学

Biochimie Pub Date : 2025-01-21 DOI: 10.1016/j.biochi.2025.01.005

Jiaqi Li , Huanhuan Sun , Huasheng Wang , Fengqiu Zhou , Wenyu Wu , Dan Chen , Zhenning Zhou , Hai Yan

{"title":"Structure and function analysis of microcystin transport protein MlrD","authors":"Jiaqi Li , Huanhuan Sun , Huasheng Wang , Fengqiu Zhou , Wenyu Wu , Dan Chen , Zhenning Zhou , Hai Yan","doi":"10.1016/j.biochi.2025.01.005","DOIUrl":"10.1016/j.biochi.2025.01.005","url":null,"abstract":"<div><div>Microorganisms play a crucial role in the degradation of microcystins (MCs), with most MC-degrading bacteria utilizing the <em>mlr</em> gene cluster (<em>mlrABCD</em>) mechanism. While previous studies have advanced our understanding of the structure, function, and degradation mechanisms of MlrA, MlrB, and MlrC, research on MlrD remains limited. Consequently, the molecular structure and specific catalytic processes of MlrD are still unclear. This study investigates MlrD from <em>Sphingopyxis</em> sp. USTB-05, utilizing bioinformatics tools for analysis and prediction, conducting homology analysis, and constructing the molecular structure of MlrD. Bioinformatics analysis suggests that MlrD is an alkaline, hydrophobic protein with good thermal stability and is likely located in the cell membrane as a membrane protein without a signal peptide. Homology analysis indicates that MlrD belongs to the PTR2 protein family and contains a PTR2 domain. Phylogenetic analysis reveals that MlrD follows both vertical and horizontal genetic transfer patterns during evolution. Homology modeling demonstrates that the three-dimensional structure of MlrD is primarily composed of 12 α-helices, with conserved residues between the <em>N</em>-terminal and <em>C</em>-terminal domains forming a large reaction cavity. This research broadens current knowledge of MC biodegradation and offers a promising foundation for future studies.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"231 ","pages":"Pages 155-162"},"PeriodicalIF":3.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026150","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

Luminescence-based complementation assay to assess target engagement and cell permeability of glycolate oxidase (HAO1) inhibitors 基于荧光的互补测定法，用于评估乙醇酸氧化酶（HAO1）抑制剂的靶参与性和细胞渗透性。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-01-01 DOI: 10.1016/j.biochi.2024.08.011

Sabrina R. Mackinnon , Tryfon Zarganes-Tzitzikas , Cassandra J. Adams , Paul E. Brennan , Wyatt W. Yue

{"title":"Luminescence-based complementation assay to assess target engagement and cell permeability of glycolate oxidase (HAO1) inhibitors","authors":"Sabrina R. Mackinnon , Tryfon Zarganes-Tzitzikas , Cassandra J. Adams , Paul E. Brennan , Wyatt W. Yue","doi":"10.1016/j.biochi.2024.08.011","DOIUrl":"10.1016/j.biochi.2024.08.011","url":null,"abstract":"<div><div>Glycolate oxidase (HAO1) catalyses the synthesis of glyoxylate, a common metabolic intermediate that causes renal failure if accumulated. HAO1 inhibition is an emerging treatment for primary hyperoxaluria, a rare disorder of glyoxylate metabolism. Here we report the first cell-based measurement of inhibitor uptake and engagement with HAO1, by adapting the cellular thermal shift assay (CETSA) based on Nano luciferase complementation and luminescence readout. By profiling the interaction between HAO1 and four well-characterised inhibitors in intact and lysed HEK293T cells, we showed that our CETSA method differentiates between low-permeability/high-engagement and high-permeability/low-engagement ligands and is able to rank HAO1 inhibitors in line with both recombinant protein methods and previously reported indirect cellular assays. Our methodology addresses the unmet need for a robust, sensitive, and scalable cellular assay to guide HAO1 inhibitor development and, in broader terms, can be rapidly adapted for other targets to simultaneously monitor compound affinity and cellular permeability.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"228 ","pages":"Pages 71-81"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997067","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