ChemBioChemPub Date : 2024-11-08DOI: 10.1002/cbic.202400756
Bingbing Chen, Zhijun Liang, Yao Gong, Wei Wu, Jiaen Huang, Jiaxi Chen, Yanmei Wang, Jun Mei, Rui Chen, Zunnan Huang, Jing Sun
{"title":"Mitochondrial Viscosity Probes: Iridium(III) Complexes Induce Apoptosis in HeLa Cells.","authors":"Bingbing Chen, Zhijun Liang, Yao Gong, Wei Wu, Jiaen Huang, Jiaxi Chen, Yanmei Wang, Jun Mei, Rui Chen, Zunnan Huang, Jing Sun","doi":"10.1002/cbic.202400756","DOIUrl":"10.1002/cbic.202400756","url":null,"abstract":"<p><p>Mitochondrial viscosity has emerged as a promising biomarker for diseases such as cancer and neurodegenerative disorders, yet accurately measuring viscosity at the subcellular level remains a significant challenge. In this study, we synthesized and characterized three cyclometalated iridium(III) complexes (Ir1-Ir3) containing 5-fluorouracil derivatives as ligands. Among these, Ir1 selectively induced apoptosis in HeLa cells by increasing mitochondrial production of reactive oxygen species (ROS), which triggered a cascade of events leading to mitochondrial dysfunction. Additionally, the fluorescence lifetime of Ir1 demonstrated high sensitivity to intracellular viscosity changes, enabling real-time fluorescence lifetime imaging microscopy (FLIM) of cellular micro-viscosity during apoptosis. These findings underscore the potential of cyclometalated Ir(III) complexes for both therapeutic and diagnostic applications at the subcellular level.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400756"},"PeriodicalIF":2.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602239","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}
ChemBioChemPub Date : 2024-11-07DOI: 10.1002/cbic.202400617
Kenwa Tamagawa, Robert E Campbell, Takuya Terai
{"title":"High-Throughput Discovery of Substrate Peptide Sequences for E3 Ubiquitin Ligases Using a cDNA Display Method.","authors":"Kenwa Tamagawa, Robert E Campbell, Takuya Terai","doi":"10.1002/cbic.202400617","DOIUrl":"10.1002/cbic.202400617","url":null,"abstract":"<p><p>Cells utilize ubiquitin as a posttranslational protein modifier to convey various signals such as proteasomal degradation. The dysfunction of ubiquitylation or following proteasomal degradation can give rise to the accumulation and aggregation of improperly ubiquitylated proteins, which is known to be a general causation of many neurodegenerative diseases. Thus, the characterization of substrate peptide sequences of E3 ligases is crucial in biological and pharmaceutical sciences. In this study, we developed a novel high-throughput screening system for substrate peptide sequences of E3 ligases using a cDNA display method, which enables covalent conjugation between peptide sequences and their corresponding cDNA sequences. First, we focused on the MDM2 E3 ligase and its known peptide substrate as a model to establish the screening method, and confirmed that cDNA display method was compatible with in vitro ubiquitylation. Then, we demonstrated identification of MDM2 substrate sequences from random libraries to identify a novel motif (VKFTGGQLA). Bioinformatics analysis of the hit sequences was performed to gain insight about endogenous substrate proteins.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400617"},"PeriodicalIF":2.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602160","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}
ChemBioChemPub Date : 2024-11-07DOI: 10.1002/cbic.202400788
Rui-Ning Li, Shi-Lu Chen
{"title":"Recent Insights into the Reaction Mechanisms of Non-Heme Diiron Enzymes Containing Oxoiron(IV) Complexes.","authors":"Rui-Ning Li, Shi-Lu Chen","doi":"10.1002/cbic.202400788","DOIUrl":"10.1002/cbic.202400788","url":null,"abstract":"<p><p>Oxoiron(IV) complexes are key intermediates in the catalytic reactions of some non-heme diiron enzymes. These enzymes, across various subfamilies, activate dioxygen to generate high-valent diiron-oxo species, which, in turn, drive the activation of substrates and mediate a variety of challenging oxidative transformations. In this review, we summarize the structures, formation mechanisms, and functions of high-valent diiron-oxo intermediates in eight representative diiron enzymes (sMMO, RNR, ToMO, MIOX, PhnZ, SCD1, AlkB, and SznF) spanning five subfamilies. We also categorize and analyze the structural and mechanistic differences among these enzymes.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400788"},"PeriodicalIF":2.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602243","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}
{"title":"Front Cover: Uracil-Selective Cross-Linking in RNA and Inhibition of miRNA Function by 2-Amino-6-vinyl-7-deazapurine Deoxynucleosides (ChemBioChem 21/2024)","authors":"Nadya Soemawisastra, Hidenori Okamura, Ahmed Mostafa Abdelhady, Kazumitsu Onizuka, Mamiko Ozawa, Fumi Nagatsugi","doi":"10.1002/cbic.202482101","DOIUrl":"https://doi.org/10.1002/cbic.202482101","url":null,"abstract":"<p>MicroRNAs (miRNAs) regulate gene expression through RNA interference. Consequently, miRNA inhibitors, such as anti-miRNA oligonucleotides (AMOs), have attracted attention for treating miRNA overexpression. In article 10.1002/cbic.202400417, Fumi Nagatsugi and co-workers demonstrate that the cross-linkable nucleoside (2-amino-7-deaza-7-propynyl-6-vinylpurine deoxyriboside; dADpVP) reacted to counter uridine with high reactivity upon duplex hybridization. Moreover, the oligonucleotide containing dADpVP targeting the miRNA binding site in mRNA 3′UTR effectively inhibit the miR21 function in cells by covalent formation.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"25 21","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202482101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142664532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ER Oxidoreductin 1-Like Activity of Cyclic Diselenides Drives Protein Disulfide Isomerase in an Electron Relay System.","authors":"Rumi Mikami, Yuya Nishizawa, Yuki Iwata, Shingo Kanemura, Masaki Okumura, Kenta Arai","doi":"10.1002/cbic.202400739","DOIUrl":"10.1002/cbic.202400739","url":null,"abstract":"<p><p>Disulfide formation generally involves a two-electron oxidation reaction between cysteine residues. Additionally, disulfide formation is an essential post-translational modification for the structural maturation of proteins. This oxidative folding is precisely controlled by an electron relay network constructed by protein disulfide isomerase (PDI), with a CGHC sequence as the redox-active site, and its family enzymes. Creating reagents that mimic the functions of these enzymes facilitates folding during chemical protein synthesis. In this study, we aimed to imitate a biological electron relay system using cyclic diselenide compounds as surrogates for endoplasmic reticulum oxidoreductin 1 (Ero1), which is responsible for the re-oxidation of PDI. Oxidized PDI (PDI<sup>ox</sup>) introduces disulfide bonds into substrate proteins, resulting in its conversion to reduced PDI (PDI<sup>red</sup>). The PDI<sup>red</sup> is then re-oxidized to PDI<sup>ox</sup> by a coexisting cyclic diselenide compound, thereby restoring the function of PDI as a disulfide-forming agent. The produced diselenol state is readily oxidized to the original diselenide state with molecular oxygen, continuously sustaining the PDI catalytic cycle. This artificial electron relay system regulating enzymatic PDI function effectively promotes the oxidative folding of disulfide-containing proteins, such as insulin - a hypoglycemic formulation - by enhancing both yield and reaction velocity.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400739"},"PeriodicalIF":2.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589577","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}
ChemBioChemPub Date : 2024-11-06DOI: 10.1002/cbic.202400791
Liang Luo, Shixia Ji, Qiong Wu, Guohua Xu, Jiajing Zhao, Yixiang Liu, Lang Chen, Maili Liu, Ling Jiang, Conggang Li
{"title":"Protein Condensates Unfold G-Quadruplex Resembling a Helicase Activity.","authors":"Liang Luo, Shixia Ji, Qiong Wu, Guohua Xu, Jiajing Zhao, Yixiang Liu, Lang Chen, Maili Liu, Ling Jiang, Conggang Li","doi":"10.1002/cbic.202400791","DOIUrl":"10.1002/cbic.202400791","url":null,"abstract":"<p><p>Membrane-less organelles, formed by liquid-liquid phase separation, participate in many vital cellular processes and have received extensive attention recently. A notable form of noncanonical nucleic acid secondary structure, G-quadruplex (G4), interacts with the scaffolding proteins in these membrane-less organelles and becomes an integral part of this condensed phase. However, the structure and stability features of the integrated G4 remain poorly characterized. Herein, we employed NMR along with other biophysical methods to investigate the conformation of a G4 within condensates formed by a disordered protein known as DDX4N1. We discovered that the human telomeric sequence MHT24, which forms a G4 structure in a non-condensed phase solution of protein DDX4N1, unfolds when it is within DDX4N1 condensates due to phase separation. Our findings provide an instance of a protein acquiring new functionality through phase separation process, which deepen our understanding of how protein condensates regulate G4 structure and their functions.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400791"},"PeriodicalIF":2.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589583","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}
ChemBioChemPub Date : 2024-11-06DOI: 10.1002/cbic.202482102
Zachary H. Paine, Mayank Sharma, Simon H. Friedman
{"title":"Cover Feature: Selective Dissolution of Calcium Pyrophosphate Dihydrate Crystals Using a Pyrophosphate Specific Receptor (ChemBioChem 21/2024)","authors":"Zachary H. Paine, Mayank Sharma, Simon H. Friedman","doi":"10.1002/cbic.202482102","DOIUrl":"https://doi.org/10.1002/cbic.202482102","url":null,"abstract":"<p>In article 10.1002/cbic.202400319, Simon H. Friedman and co-workers have shown that a di-zinc complex (green circles and purple lines) can selectively dissolve crystalline calcium pyrophosphate (blue circles and red/orange space filling structure), while minimally dissolving hydroxy apatite, the main inorganic component of bone (cyan). It is effective because the complex pre-organizes electrostatically complementary zinc ions which then displace the crystalline calcium ions. Calcium pyrophosphate is the causative agent in pseudo-gout, a disease that affects millions.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"25 21","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202482102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142664533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChemBioChemPub Date : 2024-11-05DOI: 10.1002/cbic.202400748
Canqiong Hu, Shuang Liu, Guoxia Huang, Fan Yang, Lexun Li, Cao Zhang, Shuxuan Shao, Xiaodan Deng, Qiaoling Liu
{"title":"Close Proximity of Cholesterol Anchors in Membrane Induces the Dissociation of Amphiphilic DNA Strand from Membrane Surface.","authors":"Canqiong Hu, Shuang Liu, Guoxia Huang, Fan Yang, Lexun Li, Cao Zhang, Shuxuan Shao, Xiaodan Deng, Qiaoling Liu","doi":"10.1002/cbic.202400748","DOIUrl":"10.1002/cbic.202400748","url":null,"abstract":"<p><p>Dynamic DNA nanotechnology is appealing for membrane surface engineering due to their versatility and programmability. To modulate the dynamic interactions between the DNA functional units immobilized on membrane surface, membrane-anchored DNA functional units often come into close proximity each other due to DNA base pairing, which also leads to the close contact of the hydrophobic anchors in membrane. However, whether the close contact of hydrophobic anchors induces the dissociation of amphiphilic DNA structures from membrane surface is not concerned. Herein, we utilized cholesterol-labelled single-stranded DNA (ssDNA) as a simplified amphiphilic DNA structure to investigate the stability of membrane anchored DNA strands upon the closely contact of cholesterol anchors. The close contact of cholesterol-labelled ssDNA molecules driven by toehold mediated strand displacement reaction leads to approximately 41 % membrane anchored ssDNA dissociation from membrane surface, indicating the proximal cholesterol anchors in membrane could reduce the anchoring stability of cholesterol-modified DNA strands. This work enhances our understanding of the interactions between amphiphilic DNA and membranes, and provides valuable insights for the design of future DNA constructs intended for applications involving dynamic DNA reactions on membrane surface.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400748"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581205","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}
ChemBioChemPub Date : 2024-11-05DOI: 10.1002/cbic.202400719
Ruijie Zhang, Fan Dai, Songhan Deng, Yun Zeng, Jinyang Wang, Gang Liu
{"title":"Reprogramming of Glucose Metabolism for Revisiting Hepatocellular Carcinoma Resistance to Transcatheter Hepatic Arterial Chemoembolization.","authors":"Ruijie Zhang, Fan Dai, Songhan Deng, Yun Zeng, Jinyang Wang, Gang Liu","doi":"10.1002/cbic.202400719","DOIUrl":"10.1002/cbic.202400719","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is recognized globally as one of the most lethal tumors, presenting a significant menace to patients' lives owing to its exceptional aggressiveness and tendency to recur. Transcatheter hepatic arterial chemoembolization (TACE) therapy, as a first-line treatment option for patients with advanced HCC, has been proven effective. However, it is disheartening that nearly 40 % of patients exhibit resistance to this therapy. Consequently, this review delves into the metabolic aspects of glucose metabolism to explore the underlying mechanisms behind TACE treatment resistance and to propose potentially fruitful therapeutic strategies. The ultimate objective is to present novel insights for the development of personalized treatment methods targeting HCC.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400719"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581208","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}
ChemBioChemPub Date : 2024-11-05DOI: 10.1002/cbic.202400585
Daniel Ratcliff, G. C. Danielle Sedoh, Ross D. Milton
{"title":"Cross-Coupling of Mo- and V-Nitrogenases Permits Protein-Mediated Protection from Oxygen Deactivation","authors":"Daniel Ratcliff, G. C. Danielle Sedoh, Ross D. Milton","doi":"10.1002/cbic.202400585","DOIUrl":"10.1002/cbic.202400585","url":null,"abstract":"<p>Nitrogenases catalyze dinitrogen (N<sub>2</sub>) fixation to ammonia (NH<sub>3</sub>). While these enzymes are highly sensitive to deactivation by molecular oxygen (O<sub>2</sub>) they can be produced by obligate aerobes for diazotrophy, necessitating a mechanism by which nitrogenase can be protected from deactivation. In the bacterium <i>Azotobacter vinelandii</i>, one mode of such protection involves an O<sub>2</sub>-responsive ferredoxin-type protein (“Shethna protein II”, or “FeSII”) which is thought to bind with Mo-dependent nitrogenase's two component proteins (NifH and NifDK) to form a catalytically stalled yet O<sub>2</sub>-tolerant tripartite protein complex. This protection mechanism has been reported for Mo-nitrogenase, however, <i>in vitro</i> assays with V-nitrogenase suggest that this mechanism is not universal to the three known nitrogenase isoforms. Here we report that the reductase of the V-nitrogenase (VnfH) can engage in this FeSII-mediated protection mechanism when cross-coupled with Mo-nitrogenase NifDK. Interestingly, the cross-coupling of the Mo-nitrogenase reductase NifH with the V-nitrogenase VnfDGK protein does not yield such protection.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"25 23","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581207","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}