Biological Chemistry最新文献

Bioprospecting hydroxylated chalcones in in vitro model of ischemia-reoxygenation and probing NOX4 interactions via molecular docking.

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2024-12-23 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":"https://doi.org/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":""},"PeriodicalIF":2.9,"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.

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2024-12-11 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":"https://doi.org/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":""},"PeriodicalIF":2.9,"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.

IF 2.9 4区生物学

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

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

引用次数: 0

Zinc and copper effect mechanical cell adhesion properties of the amyloid precursor protein. 锌和铜对淀粉样前体蛋白机械细胞粘附特性的影响

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2024-10-21 DOI: 10.1515/hsz-2024-0054

Alexander August, Sabrina Hartmann, Sandra Schilling, Christine Müller-Renno, Tarik Begic, Antonio J Pierik, Christiane Ziegler, Stefan Kins

{"title":"Zinc and copper effect mechanical cell adhesion properties of the amyloid precursor protein.","authors":"Alexander August, Sabrina Hartmann, Sandra Schilling, Christine Müller-Renno, Tarik Begic, Antonio J Pierik, Christiane Ziegler, Stefan Kins","doi":"10.1515/hsz-2024-0054","DOIUrl":"https://doi.org/10.1515/hsz-2024-0054","url":null,"abstract":"The amyloid precursor protein (APP) can be modulated by the binding of copper and zinc ions. Both ions bind with low nanomolar affinities to both subdomains (E1 and E2) in the extracellular domain of APP. However, the impact of ion binding on structural and mechanical trans-dimerization properties is yet unclear. Using a bead aggregation assay (BAA), we found that zinc ions increase the dimerization of both subdomains, while copper promotes only dimerization of the E1 domain. In line with this, scanning force spectroscopy (SFS) analysis revealed an increase in APP adhesion force up to three-fold for copper and zinc. Interestingly, however, copper did not alter the separation length of APP dimers, whereas high zinc concentrations caused alterations in the structural features and a decrease of separation length. Together, our data provide clear differences in copper and zinc mediated APP trans-dimerization and indicate that zinc binding might favor a less flexible APP structure. This fact is of significant interest since changes in zinc and copper ion homeostasis are observed in Alzheimer's disease (AD) and were reported to affect synaptic plasticity. Thus, modulation of APP trans-dimerization by copper and zinc could contribute to early synaptic instability in AD.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457112","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 platform for the early selection of non-competitive antibody-fragments from yeast surface display libraries. 从酵母表面展示库中早期筛选非竞争性抗体片段的平台。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2024-10-01 DOI: 10.1515/hsz-2024-0102

Léxane Fournier, Deniz Demir, Desislava Elter, Lukas Pekar, Harald Kolmar, Lars Toleikis, Stefan Becker

{"title":"A platform for the early selection of non-competitive antibody-fragments from yeast surface display libraries.","authors":"Léxane Fournier, Deniz Demir, Desislava Elter, Lukas Pekar, Harald Kolmar, Lars Toleikis, Stefan Becker","doi":"10.1515/hsz-2024-0102","DOIUrl":"https://doi.org/10.1515/hsz-2024-0102","url":null,"abstract":"In this work, we report the development of a platform for the early selection of non-competitive antibody-fragments against cell surface receptors that do not compete for binding of their natural ligand. For the isolation of such subtype of blocking antibody-fragments, we applied special fluorescence-activated cell sorting strategies for antibody fragments isolation from yeast surface display libraries. Given that most of the monoclonal antibodies approved on the market are blocking ligand-receptor interactions often leading to resistance and/or side effects, targeting allosteric sites represents a promising mechanism of action to open new avenues for treatment. To directly identify these antibody-fragments during library screening, we employed immune libraries targeting the epidermal growth factor receptor as proof of concept. Incorporating a labeled orthosteric ligand during library sorting enables the early selection of non-competitive binders and introduces an additional criterion to refine the selection of candidates exhibiting noteworthy properties. Furthermore, after sequencing, more candidates were identified compared to classical sorting based solely on target binding. Hence, this platform can significantly improve the drug discovery process by the early selection of more candidates with desired properties.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340553","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

Implications of TRPM3 and TRPM8 for sensory neuron sensitisation. TRPM3 和 TRPM8 对感觉神经元敏化的影响

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2024-10-01 Print Date: 2024-10-28 DOI: 10.1515/hsz-2024-0045

Marc Behrendt

{"title":"Implications of TRPM3 and TRPM8 for sensory neuron sensitisation.","authors":"Marc Behrendt","doi":"10.1515/hsz-2024-0045","DOIUrl":"10.1515/hsz-2024-0045","url":null,"abstract":"Sensory neurons serve to receive and transmit a wide range of information about the conditions of the world around us as well as the external and internal state of our body. Sensitisation of these nerve cells, i.e. becoming more sensitive to stimuli or the emergence or intensification of spontaneous activity, for example in the context of inflammation or nerve injury, can lead to chronic diseases such as neuropathic pain. For many of these disorders there are only very limited treatment options and in order to find and establish new therapeutic approaches, research into the exact causes of sensitisation with the elucidation of the underlying mechanisms and the identification of the molecular components is therefore essential. These components include plasma membrane receptors and ion channels that are involved in signal reception and transmission. Members of the transient receptor potential (TRP) channel family are also expressed in sensory neurons and some of them play a crucial role in temperature perception. This review article focuses on the heat-sensitive TRPM3 and the cold-sensitive TRPM8 (and TRPA1) channels and their importance in sensitisation of dorsal root ganglion sensory neurons is discussed based on studies related to inflammation and injury- as well as chemotherapy-induced neuropathy.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"405 9-10","pages":"583-599"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457113","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 tailored cytochrome P450 monooxygenase from Gordonia rubripertincta CWB2 for selective aliphatic monooxygenation. 一种来自 Gordonia rubripertincta CWB2 的定制细胞色素 P450 单加氧酶，用于选择性脂肪族单加氧作用。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2024-09-30 DOI: 10.1515/hsz-2024-0041

Fabian Peter Josef Schultes, Leon Welter, Myra Schmidtke, Dirk Tischler, Carolin Mügge

{"title":"A tailored cytochrome P450 monooxygenase from Gordonia rubripertincta CWB2 for selective aliphatic monooxygenation.","authors":"Fabian Peter Josef Schultes, Leon Welter, Myra Schmidtke, Dirk Tischler, Carolin Mügge","doi":"10.1515/hsz-2024-0041","DOIUrl":"https://doi.org/10.1515/hsz-2024-0041","url":null,"abstract":"Cytochrome P450 monooxygenases are recognized as versatile biocatalysts due to their broad reaction capabilities. One important reaction is the hydroxylation of non-activated C-H bonds. The subfamily CYP153A is known for terminal hydroxylation reactions, giving access to functionalized aliphatics. Whilst fatty derivatives may be converted by numerous enzyme classes, midchain aliphatics are seldomly accepted, a prime property of CYP153As. We report here on a new CYP153A member from the genome of the mesophilic actinobacterium Gordonia rubripertincta CWB2 as an efficient biocatalyst. The gene was overexpressed in Escherichia coli and fused with a surrogate electron transport system from Acinetobacter sp. OC4. This chimeric self-sufficient whole-cell system could perform hydroxylation and epoxidation reactions: conversions of C6-C14 alkanes, alkenes, alcohols and of cyclic compounds were observed, yielding production rates of, e.g., 2.69 mM h-1 for 1-hexanol and 4.97 mM h-1 for 1,2-epoxyhexane. Optimizing the linker compositions between the protein units led to significantly altered activity. Balancing linker length and flexibility with glycine-rich and helix-forming linker units increased 1-hexanol production activity to 350 % compared to the initial linker setup with entirely helical linkers. The study shows that strategic coupling of efficient electron supply and a selective enzyme enables previously challenging monooxygenation reactions of midchain aliphatics.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340554","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 persulfidation in plants: mechanisms and functions beyond a simple stress response. 植物中的蛋白质过硫化：超越简单应激反应的机制和功能。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2024-09-23 DOI: 10.1515/hsz-2024-0038

Anna Moseler, Stephan Wagner, Andreas J Meyer

{"title":"Protein persulfidation in plants: mechanisms and functions beyond a simple stress response.","authors":"Anna Moseler, Stephan Wagner, Andreas J Meyer","doi":"10.1515/hsz-2024-0038","DOIUrl":"https://doi.org/10.1515/hsz-2024-0038","url":null,"abstract":"Posttranslational modifications (PTMs) can modulate the activity, localization and interactions of proteins and (re)define their biological function. Understanding how changing environments can alter cellular processes thus requires detailed knowledge about the dynamics of PTMs in time and space. A PTM that gained increasing attention in the last decades is protein persulfidation, where a cysteine thiol (-SH) is covalently bound to sulfane sulfur to form a persulfide (-SSH). The precise cellular mechanisms underlying the presumed persulfide signaling in plants are, however, only beginning to emerge. In the mitochondrial matrix, strict regulation of persulfidation and H2S homeostasis is of prime importance for maintaining mitochondrial bioenergetic processes because H2S is a highly potent poison for cytochrome c oxidase. This review summarizes the current knowledge about protein persulfidation and corresponding processes in mitochondria of the model plant Arabidopsis. These processes will be compared to the respective processes in non-plant models to underpin similarities or highlight apparent differences. We provide an overview of mitochondrial pathways that contribute to H2S and protein persulfide generation and mechanisms for H2S fixation and de-persulfidation. Based on current proteomic data, we compile a plant mitochondrial persulfidome and discuss how persulfidation may regulate protein function.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280055","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

Simultaneous spectral illumination of microplates for high-throughput optogenetics and photobiology. 用于高通量光遗传学和光生物学的微孔板同步光谱照明。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2024-09-23 DOI: 10.1515/hsz-2023-0205

Arend Vogt, Raik Paulat, Daniel Parthier, Verena Just, Michal Szczepek, Patrick Scheerer, Qianzhao Xu, Andreas Möglich, Dietmar Schmitz, Benjamin R Rost, Nikolaus Wenger

{"title":"Simultaneous spectral illumination of microplates for high-throughput optogenetics and photobiology.","authors":"Arend Vogt, Raik Paulat, Daniel Parthier, Verena Just, Michal Szczepek, Patrick Scheerer, Qianzhao Xu, Andreas Möglich, Dietmar Schmitz, Benjamin R Rost, Nikolaus Wenger","doi":"10.1515/hsz-2023-0205","DOIUrl":"10.1515/hsz-2023-0205","url":null,"abstract":"The biophysical characterization and engineering of optogenetic tools and photobiological systems has been hampered by the lack of efficient methods for spectral illumination of microplates for high-throughput analysis of action spectra. Current methods to determine action spectra only allow the sequential spectral illumination of individual wells. Here we present the open-source RainbowCap-system, which combines LEDs and optical filters in a standard 96-well microplate format for simultaneous and spectrally defined illumination. The RainbowCap provides equal photon flux for each wavelength, with the output of the LEDs narrowed by optical bandpass filters. We validated the RainbowCap for photoactivatable G protein-coupled receptors (opto-GPCRs) and enzymes for the control of intracellular downstream signaling. The simultaneous, spectrally defined illumination provides minimal interruption during time-series measurements, while resolving 10 nm differences in the action spectra of optogenetic proteins under identical experimental conditions. The RainbowCap is also suitable for studying the spectral dependence of light-regulated gene expression in bacteria, which requires illumination over several hours. In summary, the RainbowCap provides high-throughput spectral illumination of microplates, while its modular, customizable design allows easy adaptation to a wide range of optogenetic and photobiological applications.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280056","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

The BCL11A transcription factor stimulates the enzymatic activities of the OGG1 DNA glycosylase BCL11A 转录因子刺激 OGG1 DNA 糖基化酶的酶活性

IF 3.7 4区生物学

Biological Chemistry Pub Date : 2024-09-14 DOI: 10.1515/hsz-2024-0088

Tetiana Petrachkova, Olha Soldatkina, Lam Leduy, Alain Nepveu

{"title":"The BCL11A transcription factor stimulates the enzymatic activities of the OGG1 DNA glycosylase","authors":"Tetiana Petrachkova, Olha Soldatkina, Lam Leduy, Alain Nepveu","doi":"10.1515/hsz-2024-0088","DOIUrl":"https://doi.org/10.1515/hsz-2024-0088","url":null,"abstract":"The BCL11A transcription factor has previously been shown to interact with and stimulate the enzymatic activities of the NTHL1 DNA glycosylase and Pol β polymerase. Here we show that BCL11A and a smaller peptide encompassing amino acids 160 to 520 can interact with the 8-oxoguanine DNA glycosylase, OGG1, increase the binding of OGG1 to DNA that contains an 8-oxoguanine base and stimulate the glycosylase activity of OGG1. Following BCL11A knockdown, we observed an increase in oxidized purines in the genome using comet assays, while immunoassays reveal an increase in 8-oxoG bases. Structure-function analysis indicates that the stimulation of OGG1 by BCL11A requires the zinc fingers 1, 2 and 3 as well as the proline-rich region between the first and second zing finger, but a glutamate-rich region downstream of zinc finger 3 is dispensable. Ectopic expression of a small peptide that contains the three zinc fingers can rescue the increase in 8-oxoguanine caused by BCL11A knockdown. These findings, together with previous results showing that BCL11A stimulates the enzymatic activities of NTHL1 and the Pol β polymerase, suggest that high expression of BCL11A is important to protect cancer cells against oxidative DNA damage.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"53 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249468","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