Archives of biochemistry and biophysics最新文献

{"title":"Differential scanning calorimetry of proteins and Zimm–Bragg model in water","authors":"","doi":"10.1016/j.abb.2024.110132","DOIUrl":"10.1016/j.abb.2024.110132","url":null,"abstract":"<div><p>Differential Scanning Calorimetry (DSC) is a regular and powerful tool to measure the specific heat profile of various materials. Hydrogen bonds play a crucial role in stabilizing the three-dimensional structure of proteins. Naturally, information about the strength of hydrogen bonds is contained in the measured DSC profiles. Despite its obvious importance, there is no approach that would allow the extraction of such information from the heat capacity measurements. In order to connect the measured profile to microscopic properties of a polypeptide chain, a proper model is required to fit. Using recent advances in the Zimm–Bragg (ZB) theory of protein folding in water, we propose a new and efficient algorithm to process the DSC experimental data and to extract the H-bonding energy among other relevant constants. Thus, for the randomly picked set of 33 proteins, we have found a quite narrow distribution of hydrogen bonding energies from 1 to 8 kJ/mol with the average energy of intra-protein hydrogen bonds <span><math><mrow><mover><mrow><mi>h</mi></mrow><mo>¯</mo></mover><mo>=</mo><mn>4</mn><mo>.</mo><mn>2</mn><mo>±</mo><mn>1</mn><mo>.</mo><mn>5</mn><mspace></mspace></mrow></math></span> kJ/mol and the average energy of water–protein bonds as <span><math><mrow><mover><mrow><msub><mrow><mi>h</mi></mrow><mrow><mi>p</mi><mi>s</mi></mrow></msub></mrow><mo>¯</mo></mover><mo>=</mo><mn>3</mn><mo>.</mo><mn>8</mn><mo>±</mo><mn>1</mn><mo>.</mo><mn>5</mn><mspace></mspace></mrow></math></span> kJ/mol. This is an important illustration of a tiny disbalance between the water–protein and intraprotein hydrogen bonds. Fitted values of the nucleation parameter <span><math><mi>σ</mi></math></span> belong to the range from 0.001 to 0.01, as expected. The reported method can be considered as complementary to the classical two-state approach and together with other parameters provides the protein–water and intraprotein H-bonding energies, not accessible within the two-state paradigm.</p></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0003986124002546/pdfft?md5=c18638a73206494f868d828c2328dfd0&pid=1-s2.0-S0003986124002546-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049004","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}

{"title":"Docosahexaenoic acid enhances the treatment efficacy for castration-resistant prostate cancer by inhibiting autophagy through Atg4B inhibition","authors":"","doi":"10.1016/j.abb.2024.110135","DOIUrl":"10.1016/j.abb.2024.110135","url":null,"abstract":"<div><p>Autophagy induction in cancer is involved in cancer progression and the acquisition of resistance to anticancer agents. Therefore, autophagy is considered a potential therapeutic target in cancer therapy. In this study, we found that long-chain fatty acids (LCFAs) have inhibitory effects on Atg4B, which is essential for autophagosome formation, through screening based on the pharmacophore of <strong>21f</strong>, a recently developed Atg4B inhibitor. Among these fatty acids, docosahexaenoic acid (DHA), a polyunsaturated fatty acid, exhibited the most potent Atg4B inhibitory activity. DHA inhibited autophagy induced by androgen receptor signaling inhibitors (ARSI) in LNCaP and 22Rv1 prostate cancer cells and significantly increased apoptotic cell death. Furthermore, we investigated the effect of DHA on resistance to ARSI by establishing darolutamide-resistant prostate cancer 22Rv1 (22Rv1/Dar) cells, which had developed resistance to darolutamide, a novel ARSI. At baseline, 22Rv1/Dar cells showed a higher autophagy level than parental 22Rv1 cells. DHA significantly suppressed Dar-induced autophagy and sensitized 22Rv1/Dar cells by inducing apoptotic cell death through mitochondrial dysfunction. These results suggest that DHA supplementation may improve prostate cancer therapy with ARSI.</p></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054755","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":"Study of the TEAD-binding domain of the VGLL1, VGLL2 and VGLL3 proteins from vertebrates","authors":"","doi":"10.1016/j.abb.2024.110136","DOIUrl":"10.1016/j.abb.2024.110136","url":null,"abstract":"<div><p>The TEAD transcription factors are the final effectors of the Hippo pathway, and to exert their transcriptional activity they need to interact with other proteins. The three paralogous vestigial-like proteins VGLL1, VGLL2 and VGLL3 bind to TEAD via a conserved short linear sequence, the Tondu motif. The TEAD-binding domain of human VGLL2 contains in addition an Ω-loop, which is also present in Vg (vestigial) from arthropods and the YAP proteins, another family of TEAD interactors. In this report, using the available structural data, we study the amino acid sequence of the TEAD-binding domain of more than 2400 putative VGLL proteins from vertebrates. This analysis shows a strong link between sequence conservation and functional role for the residues from the Tondu motif. It also reveals that one protein sequence containing both a Tondu motif and an Ω-loop is present in most (if not all) vertebrate species. This suggests that there is a selective pressure to keep a VGLL paralog with a functional Ω-loop in vertebrates. Finally, this study identifies, particularly in mammals, variants of VGLL2 and VGLL3 with an altered TEAD-binding domain suggesting that they may have a different biological function than their homologs.</p></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054757","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 stress-responsive gene ATF3 drives fibroblast activation and collagen production through transcriptionally activating TGF-β receptor Ⅱ in skin wound healing","authors":"","doi":"10.1016/j.abb.2024.110134","DOIUrl":"10.1016/j.abb.2024.110134","url":null,"abstract":"<div><p>Skin wound is an emerging health challenge on account of the high-frequency trauma, surgery and chronic refractory ulcer. Further study on the disease biology will help to develop new effective approaches for wound healing. Here, we identified a wound-stress responsive gene, activating transcription factor 3 (ATF3), and then investigated its biological action and mechanism in wound healing. In the full-thickness skin wound model, ATF3 was found to promote fibroblast activation and collagen production, resulted in accelerated wound healing. Mechanically, ATF3 transcriptionally activated TGF-β receptor Ⅱ via directly binding to its specific promoter motif, followed by the enhanced TGF-β/Smad pathway in fibroblasts. Moreover, the increased ATF3 upon skin injury was partly resulted from hypoxia stimulation with Hif-1α dependent manner. Altogether, this work gives novel insights into the biology and mechanism of stress-responsive gene ATF3 in wound healing, and provides a potential therapeutic target for treatment.</p></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054758","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":"Epigenetic regulation of Nrf2-Mediated angiogenesis in diabetic foot ulcer progression: Role of histone deacetylases","authors":"","doi":"10.1016/j.abb.2024.110133","DOIUrl":"10.1016/j.abb.2024.110133","url":null,"abstract":"<div><p>Nuclear factor E2-related factor 2 (Nrf2), a redox-sensitive transcription factor, regulates proangiogenic mediators, and antioxidant and detoxification enzymes. However, hitherto its regulation in the progression of DFU was poorly examined. The regulation of Nrf2 has been reported to be affected by various factors, including histone deacetylase (HDACs) and DNA methylation. The present study aimed to profile all classes of HDACs and correlate them with Nrf2 and angiogenic markers in the tissue biopsies of different grades of DFU patients (n = 20 in each grade). The gene expression profile of Nrf2 and its downstream targets, angiogenic markers, and all classes of HDACs were assessed using qPCR. Spearman's correlation was performed to analyze the correlation of HDACs with Nrf2 and its downstream targets along with angiogenic markers. We observed a progressive decrease in the gene expression of Nrf2 and angiogenic markers such as VEGF, HIF-1α, and SDF-1α and also an increase in the TSP-2 expression in different grades of DFU. In parallel, a significant downregulation of HDAC2/8 and SIRT1/2/4 has been observed in various grades of DFU subjects. On the other hand, HDAC1/3/4/11 and SIRT3/5/6/7 showed upregulation in different grades of DFU and the maximum increase was observed in Grade 3 patients. A significant negative correlation between Nrf2 and HDAC4, angiogenic markers, and HDAC4 suggested the pivotal role of the HDAC4-regulated Nrf2-mediated angiogenesis among DFU subjects. We have generated a first line of evidence on the epigenetic regulation of Nrf2 and its correlation with angiogenesis in the progression of diabetic foot ulcers.</p></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054756","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":"Effects of medium pH on the yeast plasma membrane potential","authors":"","doi":"10.1016/j.abb.2024.110131","DOIUrl":"10.1016/j.abb.2024.110131","url":null,"abstract":"<div><p>The effects of different pH incubation values and K⁺ on yeast plasma membrane potential (PMP) were studied both by the fluorescence changes and the accumulation of thioflavin T (ThT), a method that has been shown most adequate for both procedures. By the changes in fluorescence of ThT, the qualitative observation of PMP at the 3 evaluated pHs indicated that cells at pH 4.0 maintain a PMP lower, but close to the observed at pH 6.0 and 7.0. By measuring the accumulation of ThT and applying the Nernst equation on the different concentrations in and out, the values of PMP could also be estimated at the different pHs, resulting in values in mV, in agreement with our observations by following the fluorescence. Yeast cells at their native niches, or during fermentations must cope with low pHs, so the importance to maintain a robust PMP to survive. The contribution of bicarbonate, derived from the fermentation to the establishment of the PMP is also described. The experiments showed once more the efficacy of the methods used with this dye.</p></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0003986124002534/pdfft?md5=c64c0cfc565655a51a407a530737c36f&pid=1-s2.0-S0003986124002534-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035071","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}

{"title":"Construction of highly active and stable recombinant nattokinase by engineered bacteria and computational design","authors":"","doi":"10.1016/j.abb.2024.110126","DOIUrl":"10.1016/j.abb.2024.110126","url":null,"abstract":"<div><p>Nattokinase (NK) is an enzyme that has been recognized as a new potential thrombolytic drug due to its strong thrombolytic activity. However, it is difficult to maintain the enzyme activity of NK during high temperature environment of industrial production. In this study, we constructed six NK mutants with potential for higher thermostability using a rational protein engineering strategy integrating free energy-based methods and molecular dynamics (MD) simulation. Then, wild-type NK and NK mutants were expressed in <em>Escherichia coli</em> (<em>E. coli</em>), and their thermostability and thrombolytic activity were tested. The results showed that, compared with wild-type NK, the mutants Y256P, Q206L and E156F all had improved thermostability. The optimal mutant Y256P showed a higher melting temperature (<em>T</em>_m) of 77.4 °C, an increase of 4 °C in maximum heat-resistant temperature and an increase of 51.8 % in activity at 37 °C compared with wild-type NK. Moreover, we also explored the mechanism of the increased thermostability of these mutants by analysing the MD trajectories under different simulation temperatures.</p></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999346","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":"Complement Factor B (CFB) inhibits the malignant progression of lung adenocarcinoma by downregulating the Ras/MAPK signaling pathway","authors":"","doi":"10.1016/j.abb.2024.110130","DOIUrl":"10.1016/j.abb.2024.110130","url":null,"abstract":"<div><p>Lung adenocarcinoma (LUAC) as the most common lung cancer, and its incidence is increasing. Complement factor B (CFB) is an important factor in the alternative complement pathway. CFB has been reported to be involved in the progression of many cancers, including in pancreatic cancer, cutaneous squamous cell carcinoma, and nasopharyngeal carcinoma, but the function and molecular mechanism of CFB in LUAC remains unclear. The present study aimed to explore the role of CFB in LUAC malignant progression. In our previous study, we found that CFB was downregulated expression in LUAC clinical samples. Here, we firstly detected the cell function <em>in vitro</em>. Cell proliferation and migration were increased, while cell apoptosis and cell cycle arrest were suppressed after CFB knockdown. Overexpression of CFB repressed the malignant progression of LUAC <em>in vitro</em>. Besides, <em>in vivo</em> experiments revealed that upregulation of CFB inhibited tumor growth and Ki67 expression. Additionally, our data indicated that CFB negatively regulated Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, upregulation of CFB inhibited the progression of LUAC was reversed by Ras/MAPK pathway activators (ML-098 or C16-PAF). Our study uncovered that CFB acts as a tumor suppressor repressed tumorigenesis of LUAC through inhibiting the Ras/MAPK pathway, suggesting that CFB may be a potential biomarker and therapeutic target for LUAC.</p></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0003986124002522/pdfft?md5=0f88b81811eae76c695d0efdfc41a615&pid=1-s2.0-S0003986124002522-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035070","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}

{"title":"Exploring the anti-protozoal mechanisms of Syzygium aromaticum phytochemicals targeting Cryptosporidium parvum lactate dehydrogenase through molecular dynamics simulations","authors":"","doi":"10.1016/j.abb.2024.110124","DOIUrl":"10.1016/j.abb.2024.110124","url":null,"abstract":"<div><p><em>Cryptosporidium parvum</em> (<em>C. parvum</em>), a protozoan parasite, is known to induce significant gastrointestinal disease in humans. Lactate dehydrogenase (LDH), a protein of <em>C. parvum</em>, has been identified as a potential therapeutic target for developing effective drugs against infection. This study utilized a computational drug discovery approach to identify potential drug molecules against the LDH protein of <em>C. parvum</em>. In the present investigation, we conducted a structure-based virtual screening of 55 phytochemicals from the <em>Syzygium aromaticum</em> (<em>S. aromaticum</em>). This process identified four phytochemicals, including Gallotannin 23, Eugeniin, Strictinin, and Ellagitannin, that demonstrated significant binding affinity and dynamic stability with LDH protein. Interestingly, these four compounds have been documented to possess antibacterial, antiviral, anti-inflammatory, and antioxidant properties. The docked complexes were simulated for 100 ns using Desmond to check the dynamic stability. Finally, the free binding energy was computed from the last 10ns MD trajectories. Gallotannin 23 and Ellagitannin exhibited considerable binding affinity and stability with the target protein among all four phytochemicals. These findings suggest that these predicted phytochemicals from <em>S. aromaticum</em> could be further explored as potential hit candidates for developing effective drugs against <em>C. parvum</em> infection. The in vitro and in vivo experimental validation is still required to confirm their efficacy and safety as LDH inhibitors.</p></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999347","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":"LncRNA ZNF649-AS1 promotes trastuzumab resistance and TAM-dependent PD-L1 expression in breast cancer by regulating EXOC7 alternative splicing","authors":"","doi":"10.1016/j.abb.2024.110128","DOIUrl":"10.1016/j.abb.2024.110128","url":null,"abstract":"<div><h3>Background</h3><p>Trastuzumab resistance is a serious clinical problem in the treatment of HER2-positive breast cancer (BC). The lncRNA ZNF649-AS1 was previously found to promote HER2-positive BC trastuzumab resistance. The study aims to explore the molecular mechanism of ZNF649-AS1 in HER2-positive BC trastuzumab resistance.</p></div><div><h3>Methods</h3><p>Tumor tissue and peripheral blood samples were collected from 20 HER2-positive BC patients with trastuzumab-resistant and non-resistant, respectively. Trastuzumab-resistant BC cell lines SKBR-3-TR and BT474-TR were established. RIP was employed to confirm the binding of ZNF649-AS1, PRPF8 and exocyst complex component 7 (EXOC7). RNA expression of EXOC7-L (Full length of EXOC7) and EXOC7-S (Spliceosome of EXOC7) were detected using agarose gel electrophoresis. Expressions of macrophage markers CD68⁺ CD206⁺ were measured by flow cytometry.</p></div><div><h3>Results</h3><p>ZNF649-AS1 expression was upregulated in HER2-positive BC trastuzumab resistance. ZNF649-AS1 downregulation inhibited trastuzumab resistance in HER2-positive BC. ZNF649-AS1 regulated EXOC7 alternative splicing by binding with PRPF8. EXOC7-S knockdown suppressed trastuzumab resistance and TAM-dependent PD-L1 expression in HER2-positive BC. EXOC7-S overexpression abolished the effects of ZNF649-AS1 knockdown on trastuzumab resistance and TAM-dependent PD-L1 expression in HER2-positive BC.</p></div><div><h3>Conclusion</h3><p>ZNF649-AS1 promoted trastuzumab resistance and TAM-dependent PD-L1 expression in HER2-positive BC via promoting alternative splicing of EXOC7 by PRPF8.</p></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003481","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}