Biological Chemistry最新文献_第2页

Time- and dose-dependent effects of CIGB-300 on the proteome of lung squamous cell carcinoma. CIGB-300对肺鳞状细胞癌蛋白质组的时间和剂量依赖性影响。

IF 2.4 4区生物学

Biological Chemistry Pub Date : 2025-04-23 Print Date: 2025-03-26 DOI: 10.1515/hsz-2024-0149

Liudy García-Hernández, Lingfeng Dai, Arielis Rodríguez-Ulloa, Ying Yi, Luis J González, Vladimir Besada, Wen Li, Silvio E Perea, Yasser Perera

{"title":"Time- and dose-dependent effects of CIGB-300 on the proteome of lung squamous cell carcinoma.","authors":"Liudy García-Hernández, Lingfeng Dai, Arielis Rodríguez-Ulloa, Ying Yi, Luis J González, Vladimir Besada, Wen Li, Silvio E Perea, Yasser Perera","doi":"10.1515/hsz-2024-0149","DOIUrl":"10.1515/hsz-2024-0149","url":null,"abstract":"Proteome-wide scale in a dose- and time-depending setting is crucial to fully understand the pharmacological mechanism of anticancer drugs as well as identification of candidates for drug response biomarkers. Here, we investigated the effect of the CIGB-300 anticancer peptide at IC50 and IC80 doses during 1 and 4 h of treatment on the squamous lung cancer cell (NCI-H226) proteome. An overwhelming dose-dependent inhibitory effect with minor up-regulated proteins was observed by increasing CIGB-300 dose level. Functional enrichment was also CIGB-300 dose-dependent with common or exclusively regulated proteins in each dose and time settings. A protein core involving small molecule biosynthesis, aldehyde metabolism and metabolism of nucleobases was regulated irrespectively to the dose or the treatment time. Importantly, a group of proteins linked to NSCLC tumor biology, poor clinical outcome and some Protein Kinase CK2 substrates, were significantly regulated by treating with both CIGB-300 doses. Likewise, we observed a consistent downregulation of different proteins that had been already reported to be inhibited by CIGB-300 in lung adenocarcinoma and acute myeloid leukemia. Overall, our proteomics-guided strategy based on time and drug dose served to uncover novel clues supporting the CIGB-300 cytotoxic effect and also to identify putative pharmacodynamic biomarkers in NSCLC.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"89-100"},"PeriodicalIF":2.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

A CK2α' mutant indicating why CK2α and CK2α', the isoforms of the catalytic subunit of human protein kinase CK2, deviate in affinity to CK2β. 人类蛋白激酶CK2催化亚基的同工型CK2α和CK2α′对CK2β的亲和力偏离的原因是CK2α突变体。

IF 2.4 4区生物学

Biological Chemistry Pub Date : 2025-04-14 Print Date: 2025-03-26 DOI: 10.1515/hsz-2024-0157

Christian Werner, Sophia Eimermacher, Hugo Harasimowicz, Dietmar Fischer, Markus Pietsch, Karsten Niefind

{"title":"A CK2α' mutant indicating why CK2α and CK2α', the isoforms of the catalytic subunit of human protein kinase CK2, deviate in affinity to CK2β.","authors":"Christian Werner, Sophia Eimermacher, Hugo Harasimowicz, Dietmar Fischer, Markus Pietsch, Karsten Niefind","doi":"10.1515/hsz-2024-0157","DOIUrl":"10.1515/hsz-2024-0157","url":null,"abstract":"Protein kinase CK2 (casein kinase 2) mainly exists as heterotetrameric holoenzyme with two catalytic subunits (CK2α or CK2α') bound to a homodimer of non-catalytic subunits (CK2β). With CSNK2A1 and CSNK2A2, the human genome contains two paralogs encoding catalytic CK2 subunits. Both gene products, called CK2α and CK2α', strongly interact with CK2β. An earlier report that CK2α' has a lower CK2β affinity than CK2α is confirmed via isothermal titration calorimetry in this study. Furthermore, we show with a fluorescence-anisotropy assay that a CK2β-competitive peptide binds less strongly to CK2α' than to CK2α. The reason for the reduced affinity of CK2α' to CK2β and CK2β competitors is puzzling: both isoenzymes have identical amino acid compositions at their CK2β interfaces, but the β4β5 loop, a component of this interface, is conformationally less adaptable in CK2α' than in CK2α due to intramolecular constraints. To release these constraints, we constructed a CK2α' mutant that was equalized to CK2α at the backside of the β4β5 loop. Concerning thermostability, affinity to CK2β or CK2β competitors and 3D-structure next to the β4β5 loop, this CK2α' mutant is more similar to CK2α than to its own wild-type, suggesting a critical role of the β4β5 loop adaptability for CK2β affinity.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"101-115"},"PeriodicalIF":2.4,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Exploring the biological potential of the brominated indenoindole MC11 and its interaction with protein kinase CK2. 探索溴化吲哚 MC11 的生物潜力及其与蛋白激酶 CK2 的相互作用。

IF 2.4 4区生物学

Biological Chemistry Pub Date : 2025-03-24 Print Date: 2025-03-26 DOI: 10.1515/hsz-2024-0160

Christelle Marminon, Christian Werner, Alexander Gast, Lars Herfindal, Johana Charles, Dirk Lindenblatt, Dagmar Aichele, Angélique Mularoni, Stein Ove Døskeland, Joachim Jose, Karsten Niefind, Marc Le Borgne

{"title":"Exploring the biological potential of the brominated indenoindole MC11 and its interaction with protein kinase CK2.","authors":"Christelle Marminon, Christian Werner, Alexander Gast, Lars Herfindal, Johana Charles, Dirk Lindenblatt, Dagmar Aichele, Angélique Mularoni, Stein Ove Døskeland, Joachim Jose, Karsten Niefind, Marc Le Borgne","doi":"10.1515/hsz-2024-0160","DOIUrl":"10.1515/hsz-2024-0160","url":null,"abstract":"Protein kinase CK2 is a promising therapeutic target, especially in oncology. Over the years, various inhibitors have been developed, with polyhalogenated scaffolds emerging as a particularly effective class. Halogens like bromine and chlorine enhance inhibitor stability by forming additional interactions within the ATP pocket. Among halogenated scaffolds, benzotriazole and benzimidazole have led to potent molecules such as 4,5,6,7-tetrabromo-1H-benzotriazole (IC50 = 300 nM) and 4,5,6,7-tetrabromo-2-(dimethylamino)benzimidazole (IC50 = 140 nM). Modifications, including 4,5,6-tribromo-7-ethyl-1H-benzotriazole (IC50 = 160 nM), further improved activity. Changing scaffolds while retaining halogens has enabled design of new inhibitors. Flavonols, dibenzofuranones, and the indeno[1,2-b]indole scaffold are key examples. Halogenation of the reference molecule 5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione (4b, IC50 = 360 nM) significantly boosted potency. The study focused on introducing four halogens, yielding to the compound 1,2,3,4-tetrabromo-5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione (MC11), with an IC50 of 16 nM. Co-crystallography revealed how bromine atoms enhance binding, and MC11 demonstrated strong in cellulo activity, particularly against leukemic cell lines like IPC-Bcl2.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"125-138"},"PeriodicalIF":2.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

GPI-anchored serine proteases: essential roles in development, homeostasis, and disease. gpi锚定丝氨酸蛋白酶：在发育、体内平衡和疾病中的重要作用。

IF 2.4 4区生物学

Biological Chemistry Pub Date : 2025-03-17 Print Date: 2025-01-29 DOI: 10.1515/hsz-2024-0135

Joseph G Lundgren, Michael G Flynn, Karin List

引用次数: 0

Broadened substrate specificity of bacterial dipeptidyl-peptidase 7 enables release of half of all dipeptide combinations from peptide N-termini. 细菌二肽基肽酶7扩大了底物特异性，使一半的二肽组合从肽n端释放出来。

IF 2.4 4区生物学

Biological Chemistry Pub Date : 2025-02-10 Print Date: 2025-01-29 DOI: 10.1515/hsz-2024-0156

Kana Shirakura, Takayuki K Nemoto, Yuko Ohara Nemoto, Haruka Nishimata, Momo Sawase, Yu Shimoyama, Manami Nakasato-Suzuki, Kiyoshi Ito, Naomi Tanoue

{"title":"Broadened substrate specificity of bacterial dipeptidyl-peptidase 7 enables release of half of all dipeptide combinations from peptide N-termini.","authors":"Kana Shirakura, Takayuki K Nemoto, Yuko Ohara Nemoto, Haruka Nishimata, Momo Sawase, Yu Shimoyama, Manami Nakasato-Suzuki, Kiyoshi Ito, Naomi Tanoue","doi":"10.1515/hsz-2024-0156","DOIUrl":"10.1515/hsz-2024-0156","url":null,"abstract":"Dipeptide production mediated by dipeptidyl-peptidase (DPP)4, DPP5, DPP7, and DPP11 plays a crucial role in growth of Porphyromonas gingivalis, a periodontopathic asaccharolytic bacterium. Given the particular P1-position specificity of DPPs, it has been speculated that DPP5 or DPP7 might be responsible for degrading refractory P1 amino acids, i.e., neutral (Thr, His, Gly, Ser, Gln) and hydrophilic (Asn) residues. The present results identified DPP7 as an entity that processes these residues, thus ensuring complete production of nutritional dipeptides in the bacterium. Activity enhancement by the P1' residue was observed in DPP7, as well as DPP4 and DPP5. Toward the refractory P1 residues, DPP7 uniquely hydrolyzed HX|LD-MCA (X = His, Gln, or Asn) and their hydrolysis was most significantly suppressed in dpp7 gene-disrupted cells. Additionally, hydrophobic P2 residue significantly enhanced DPP7 activity toward these substrates. The findings propose a comprehensive 20 P1 × 20 P2 amino acid matrix showing the coordination of four DPPs to achieve complete dipeptide production along with subsidiary peptidases. The present finding of a broad substrate specificity that DPP7 accounts for releasing 48 % (192/400) of N-terminal dipeptides could implicate its potential role in linking periodontopathic disease to related systemic disorders.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"51-64"},"PeriodicalIF":2.4,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Protein kinase CK2 contributes to glucose homeostasis. 蛋白激酶CK2有助于葡萄糖稳态。

IF 2.4 4区生物学

Biological Chemistry Pub Date : 2025-02-07 Print Date: 2025-03-26 DOI: 10.1515/hsz-2024-0158

Claudia Götz, Mathias Montenarh

{"title":"Protein kinase CK2 contributes to glucose homeostasis.","authors":"Claudia Götz, Mathias Montenarh","doi":"10.1515/hsz-2024-0158","DOIUrl":"10.1515/hsz-2024-0158","url":null,"abstract":"In the early days of CK2 research, it was already published that the affinity of CK2 for its substrate casein was affected by insulin. Subsequent to the discovery of inhibitors of CK2 kinase activity, it was shown that CK2 has an influence on hormones that regulate glucose homeostasis and on enzymes that influence glucose metabolism in pancreatic islet cells as well as in hormone-sensitive target cells. This regulation includes the influence on transcription factors and thereby, gene expression, as well as direct modulation of the catalytic activity. The used CK2 inhibitors, especially the older ones, show a broad range of specificity, selectivity and off-target effects. Recently applied methods to down-regulate the expression of individual CK2 subunits using siRNA or CRISPR/Cas9 technology have contributed to the improvement of specificity. It was shown that inhibition of CK2 kinase activity or knock-down or knock-out of CK2α leads to an elevated synthesis and secretion of insulin in pancreatic β-cells and a down-regulation of the synthesis and secretion of glucagon from pancreatic α-cells. In the present review CK2-dependent molecular mechanisms will be addressed which contribute to the maintenance of glucose homeostasis.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"69-80"},"PeriodicalIF":2.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Revival of the Escherichia coli heat shock response after two decades with a small Hsp in a critical but distinct act. 大肠杆菌热休克反应在小热休克二十年后的复苏是一个关键但独特的行为。

IF 2.4 4区生物学

Biological Chemistry Pub Date : 2025-01-07 Print Date: 2025-01-29 DOI: 10.1515/hsz-2024-0140

Tsukumi Miwa, Hideki Taguchi

引用次数: 0

Bioprospecting hydroxylated chalcones in in vitro model of ischemia-reoxygenation and probing NOX4 interactions via molecular docking. 羟基查尔酮在体外缺血-再氧化模型中的生物探测及NOX4分子对接的相互作用。

IF 2.4 4区生物学

Biological Chemistry Pub Date : 2024-12-23 Print Date: 2024-12-17 DOI: 10.1515/hsz-2024-0068

Arif Ali, Igor Moreira de Almeida, Emanuel Paula Magalhães, Jesyka Macedo Guedes, Francisco Ferdinando Mesquita Cajazeiras, Marcia Machado Marinho, Emmanuel Silva Marinho, Ramon Róseo Paula Pessoa Bezerra de Menezes, Tiago Lima Sampaio, Hélcio Silva Dos Santos, Geraldo Bezerra da Silva Júnior, Alice Maria Costa Martins

{"title":"Bioprospecting hydroxylated chalcones in in vitro model of ischemia-reoxygenation and probing NOX4 interactions via molecular docking.","authors":"Arif Ali, Igor Moreira de Almeida, Emanuel Paula Magalhães, Jesyka Macedo Guedes, Francisco Ferdinando Mesquita Cajazeiras, Marcia Machado Marinho, Emmanuel Silva Marinho, Ramon Róseo Paula Pessoa Bezerra de Menezes, Tiago Lima Sampaio, Hélcio Silva Dos Santos, Geraldo Bezerra da Silva Júnior, Alice Maria Costa Martins","doi":"10.1515/hsz-2024-0068","DOIUrl":"10.1515/hsz-2024-0068","url":null,"abstract":"Ischemia/reperfusion injury (I/R) is a leading cause of acute kidney injury (AKI) in conditions like kidney transplants, cardiac surgeries, and nephrectomy, contributing to high global mortality and morbidity. This study aimed to analyze the protective effects of 2'-hydroxychalcones in treating I/R-induced AKI by targeting key pathological pathways. Considering strong antioxidant action along with other pharmacological roles of chalcone derivatives, six 2'-hydroxychalcones were synthesized via Claisen-Schmidt condensation and analyzed for their protective effects in an I/R induced AKI model using HK-2 cells. Among six 2'-hydroxychalcones, chalcone A4 significantly increased the HK-2 cells viability compared to I/R group. Chalcone A4 reduced the cell death events by reducing generation of cytoplasmic ROS and mitochondrial transmembrane potential. It also increased GSH and SOD activity while reducing TBARS levels, indicating strong antioxidant action. Scanning electron microscope images showed that chalcone A4 reversed I/R-induced morphological changes in HK-2 cells, including apoptotic blebbing and cytoplasmic fragmentation. Furthermore, in silico studies revealed interactions with NADPH oxidase 4, further supporting its protective role in I/R-induced AKI. These results showed that chalcone A4 possess potential protective action against I/R induced cellular damage possibly due to its strong antioxidant action and potential interaction with NOX4 subunit of NADPH oxidase.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"727-743"},"PeriodicalIF":2.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Analysis of kallikrein-related peptidase 7 (KLK7) autolysis reveals novel protease and cytokine substrates. 分析钾化钾素相关肽酶7 （KLK7）自溶揭示了新的蛋白酶和细胞因子底物。

IF 2.4 4区生物学

Biological Chemistry Pub Date : 2024-12-11 Print Date: 2025-01-29 DOI: 10.1515/hsz-2024-0127

Swapnil V Ghodge, Robert A Lazarus

{"title":"Analysis of kallikrein-related peptidase 7 (KLK7) autolysis reveals novel protease and cytokine substrates.","authors":"Swapnil V Ghodge, Robert A Lazarus","doi":"10.1515/hsz-2024-0127","DOIUrl":"10.1515/hsz-2024-0127","url":null,"abstract":"Kallikrein-related peptidase 7 (KLK7) is one of 15 members of the tissue kallikrein family and is primarily expressed in the skin epidermis. The activity of KLK7 is tightly regulated by multiple stages of maturation and reversible inhibition, similar to several other extracellular proteases. In this work, we used protease-specific inhibitors and active site variants to show that KLK7 undergoes autolysis at two separate sites in the 170 and 99 loops (chymotrypsinogen numbering), resulting in a loss of enzymatic activity. A protein BLAST search using the autolyzed KLK7 loop sequences identified mast cell chymase as a potential KLK7 substrate. Indeed, KLK7 cleaves chymase resulting in a concomitant loss of activity. We further demonstrate that KLK7 can hydrolyze other mast cell proteases as well as several cytokines. These cytokines belong mainly to the interferon and IL-10 families including IFN-α, IFN-β, IFN-γ, IL-28A/IFN-λ2, IL-20, IL-22, and IL-27. This is the first study to identify a possible molecular interaction link between KLK7 and mast cell proteases and cytokines. Although the precise biological implications of these findings are unclear, this study extends our understanding of the delicate balance of proteolytic regulation of enzyme activity that maintains physiological homeostasis, and facilitates further biological investigations.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"35-49"},"PeriodicalIF":2.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Carnosic acid prevents heat stress-induced oxidative damage by regulating heat-shock proteins and apoptotic proteins in mouse testis. 鼠尾草酸通过调节小鼠睾丸热休克蛋白和凋亡蛋白来预防热应激诱导的氧化损伤。

IF 2.4 4区生物学

Biological Chemistry Pub Date : 2024-12-06 Print Date: 2024-12-17 DOI: 10.1515/hsz-2023-0374

Sirui Liu, Jiaxin Wu, Wanqing Liang, Yinkun Liu, Shuangshuang Wan, Shu Tang

引用次数: 0