RSC Chemical Biology最新文献_第3页

Deciphering protein long-chain S-acylation using mass spectrometry proteomics strategies 利用质谱法蛋白质组学策略破译蛋白质长链s -酰化。

IF 3.1

RSC Chemical Biology Pub Date : 2025-09-08 DOI: 10.1039/D5CB00146C

Anneroos E. Nederstigt, Samiksha Sardana and Marc P. Baggelaar

{"title":"Deciphering protein long-chain S-acylation using mass spectrometry proteomics strategies","authors":"Anneroos E. Nederstigt, Samiksha Sardana and Marc P. Baggelaar","doi":"10.1039/D5CB00146C","DOIUrl":"10.1039/D5CB00146C","url":null,"abstract":"Protein long-chain S-acylation, the reversible attachment of fatty acids such as palmitate to cysteine residues via thioester bonds, is a widespread post-translational modification that plays a crucial role in regulating protein localization, trafficking, and stability. Despite its prevalence and biological relevance, the study of long-chain S-acylation has long lagged behind that of other dynamic PTMs due to the hydrophobic nature and lability of the lipid modification, which complicate conventional proteomic workflows. Recent advances in mass spectrometry-based strategies have significantly expanded the toolbox for studying long-chain S-acylation, with improved workflows enabling more sensitive, site-specific, and quantitative analysis. This review summarizes key developments from the past decade across both direct and indirect mass spectrometry-based strategies, including acyl-biotin exchange, lipid metabolic labeling, and novel enrichment and fragmentation methods. We also highlight emerging challenges in distinguishing lipid-specific modifications, achieving robust quantification, and mitigating artifacts from in vitro systems, while outlining future directions to advance functional and therapeutic exploration of the S-acyl-(prote)ome.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 10","pages":" 1532-1545"},"PeriodicalIF":3.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12426770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Photoresponsive molecular tweezers modulate Taspase 1 activity. 光响应分子镊子调节脱氢酶1活性。

IF 3.1

RSC Chemical Biology Pub Date : 2025-09-05 DOI: 10.1039/d5cb00069f

Antonio L Figueroa Bietti, Alisa-Maite A Kauth, Katrin Hommel, Mike Blueggel, Laurenz Mohr, Felix C Niemeyer, Christine Beuck, Peter Bayer, Shirley K Knauer, Bart Jan Ravoo, Thomas Schrader

{"title":"Photoresponsive molecular tweezers modulate Taspase 1 activity.","authors":"Antonio L Figueroa Bietti, Alisa-Maite A Kauth, Katrin Hommel, Mike Blueggel, Laurenz Mohr, Felix C Niemeyer, Christine Beuck, Peter Bayer, Shirley K Knauer, Bart Jan Ravoo, Thomas Schrader","doi":"10.1039/d5cb00069f","DOIUrl":"10.1039/d5cb00069f","url":null,"abstract":"Light serves as an exceptional stimulus for the precise spatiotemporal regulation of protein activity and protein-protein interactions. Here, we introduce a light-responsive supramolecular ligand system designed to modulate Taspase 1, a protease critical for embryogenesis and implicated in tumor progression. Our approach utilizes photoswitchable divalent molecular tweezers engineered to target lysine-rich regions within the Taspase 1 loop. By incorporating arylazopyrazole (AAP) photoswitches, we achieve dynamic and reversible control of ligand binding. These photoswitches exhibit high photostationary states, excellent reversibility, and prolonged thermal stability of the Z isomer, ensuring reliable switching without photodegradation. The tweezer distance varies between E and Z isomers, enabling tunable binding interactions. Through a combination of surface plasmon resonance, enzymatic cleavage assays, and molecular dynamics simulations, we demonstrate that these ligands bind Taspase 1 with low micromolar affinity and effectively inhibit its proteolytic activity. While isomerization did not significantly affect the inhibition of protein-protein interaction, the E-isomers of larger tweezers exhibited powerful enzyme inhibition, likely due to their ability to bridge lysines flanking the active site. This photoswitchable tweezer system provides a versatile tool for light-controlled modulation of protein function, offering new opportunities for selectively targeting lysine-rich proteins in dynamic biological environments.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

¹⁹F NMR-tags for peptidyl prolyl conformation analysis. 19F核磁共振标签用于肽基脯氨酸构象分析。

IF 3.1

RSC Chemical Biology Pub Date : 2025-09-04 DOI: 10.1039/d5cb00118h

George S M Hanson, Faidra Batsaki, Teagan L Myerscough, Kristin Piché, Ariel Louwrier, Christopher R Coxon

{"title":"19F NMR-tags for peptidyl prolyl conformation analysis.","authors":"George S M Hanson, Faidra Batsaki, Teagan L Myerscough, Kristin Piché, Ariel Louwrier, Christopher R Coxon","doi":"10.1039/d5cb00118h","DOIUrl":"10.1039/d5cb00118h","url":null,"abstract":"Proline cis/trans isomerism plays an important role in protein folding and mediating protein-protein interactions in short linear interacting motifs within intrinsically disordered protein regions. The slow exchange rate between cis and trans prolyl bonds provides distinct signals in 19F NMR analysis of fluorinated peptides, allowing for simple quantification of each population. However, fluorine is not naturally found in proteins but can be introduced using chemical tags. In this study, we evaluate a range of fluorinated cysteine-reactive 19F NMR tags to assess their ability to react with short, linear proline-containing peptides and accurately report on the equilibrium cis/trans-Pro populations. Several fluorinated electrophilic tags, including nitrobenzenes, sulfonylpyrimidines, and acrylamides, were found to react chemoselectively and reliably report on the %cis-Pro in the model peptide Ac-LPAAC. Other 19F NMR tags were found to be poor reporters of local proline conformation. Although pentafluoropyridine was non-chemoselective, it still reliably reported on %cis-Pro when conjugated via cysteine or tyrosine in Ac-LPAAX (X = Cys, Tyr, Lys) peptides. 3,4-Difluoronitrobenzene was found to be compatible with protein tagging, albeit it had modest reactivity and afforded a pair of regioisimeric tagging-products when reacted with a cysteine mutant of α-synuclein. These tools may be valuable for probing cis/trans-Pro populations in proteins.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biosynthesis of sydonol reveals a new bisabolene cyclase and an unusual P450 aromatase. 糖醇的生物合成揭示了一个新的双abolene环化酶和一个不寻常的P450芳香化酶。

IF 3.1

RSC Chemical Biology Pub Date : 2025-09-04 DOI: 10.1039/d5cb00213c

Peiyu Lu, Ling Liu

引用次数: 0

Plasma membrane labelling efficiency, internalization and partitioning of functionalized fluorescent lipids as a function of lipid structure 质膜标记效率，内化和分配功能化荧光脂作为脂质结构的功能。

IF 3.1

RSC Chemical Biology Pub Date : 2025-09-01 DOI: 10.1039/D5CB00116A

Erdinc Sezgin

引用次数: 0

The bacterial stress response polymerase DinB tolerates sugar modifications and preferentially incorporates arabinosyl nucleotides 细菌应激反应聚合酶DinB耐受糖修饰并优先结合阿拉伯糖基核苷酸。

IF 3.1

RSC Chemical Biology Pub Date : 2025-09-01 DOI: 10.1039/D5CB00100E

Christina M. Hurley, Jeffrey M. Kubiak, Michael B. Cory, Jared B. Parker, Christian E. Loo, Laura C. Wang and Rahul M. Kohli

{"title":"The bacterial stress response polymerase DinB tolerates sugar modifications and preferentially incorporates arabinosyl nucleotides","authors":"Christina M. Hurley, Jeffrey M. Kubiak, Michael B. Cory, Jared B. Parker, Christian E. Loo, Laura C. Wang and Rahul M. Kohli","doi":"10.1039/D5CB00100E","DOIUrl":"10.1039/D5CB00100E","url":null,"abstract":"The bacterial DNA damage (SOS) response promotes DNA repair, DNA damage tolerance, and survival in the setting of genotoxic stress, including stress induced by antibiotics. In E. coli, translesion DNA synthesis can be fulfilled by Y-family DNA polymerases, including DNA polymerase IV (DinB). DinB features a more open active site and lacks proofreading ability, promoting error-prone replication. While DinB is known to tolerate damaged nucleobases like 8-oxo-guanine (8-oxoG), its ability to accommodate sugar-modified nucleotides has been underexplored, a question of importance given that such analogs are commonly used to inhibit viral and other polymerases. To explore DinB's selectivity, we screened a variety of sugar-modified noncanonical nucleotide triphosphates (nNTPs) and determined that DinB is intolerant of most 3′-modifications but can incorporate a subset of 2′-modifications. In particular, arabinosyl nucleotide triphosphates (araNTPs) showed efficient incorporation and limited extension. Furthermore, araNTPs can effectively compete with natural nucleotide triphosphates leading to stalled replication by DinB. We show that this tolerance extends to combined nucleobase and sugar modifications, with preferred misincorporation of 2′-fluoroarabinosyl-8-oxo-GTP opposite A more than C. Overall, our work highlights the potential for exploiting substrate promiscuity to target DinB and, thereby, slow bacterial adaptation to antibiotics.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 10","pages":" 1650-1656"},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12415624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural basis of SIRT2 pre-catalysis NAD⁺ binding dynamics and mechanism. SIRT2预催化NAD+结合动力学及机制的结构基础。

IF 3.1

RSC Chemical Biology Pub Date : 2025-09-01 DOI: 10.1039/d5cb00169b

Nan Zhang, Kah Chee Pow, Lanfang Chen, Quan Hao

引用次数: 0

Contributions of β-lactamase substrate specificity and outer membrane permeability to the antibiotic sheltering of β-lactam-susceptible bacteria. β-内酰胺酶底物特异性和外膜通透性对β-内酰胺敏感菌的抗生素庇护作用的贡献。

IF 3.1

RSC Chemical Biology Pub Date : 2025-08-26 DOI: 10.1039/d5cb00092k

Montserrat Mora-Ochomogo, Mitchell A Jeffs, Josephine L Liu, Christopher T Lohans

{"title":"Contributions of β-lactamase substrate specificity and outer membrane permeability to the antibiotic sheltering of β-lactam-susceptible bacteria.","authors":"Montserrat Mora-Ochomogo, Mitchell A Jeffs, Josephine L Liu, Christopher T Lohans","doi":"10.1039/d5cb00092k","DOIUrl":"10.1039/d5cb00092k","url":null,"abstract":"The use of β-lactam antibiotics is threatened by antibiotic resistant bacteria that produce β-lactamases. These enzymes not only protect the bacteria that produce them but also shelter other bacteria in the same environment that would otherwise be susceptible. While this phenomenon is of clinical significance, many of the factors that contribute to β-lactamase-mediated antibiotic sheltering have not been well-studied. We report the development of a luminescence assay to directly monitor the survival of β-lactam-susceptible bacteria in the presence of β-lactamase-producing bacteria and β-lactam antibiotics. This method provides a rapid and scalable means of quantifying antibiotic sheltering in mixed microbial populations. We applied this assay to investigate the contributions of several factors to sheltering, including the class of β-lactam, the substrate specificity of the β-lactamase, and the cell wall permeability of the β-lactamase-producing bacterium. Our results show that the extent of sheltering that occurs not only depends on the particular combination of β-lactam and β-lactamase, but is also greatly impacted by the ability of a β-lactamase to access its β-lactam substrates.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reductively activated CPP-PROTAC nanocomplexes enhance target degradation via efficient cellular uptake. 还原性活化的CPP-PROTAC纳米复合物通过有效的细胞摄取增强目标降解。

IF 3.1

RSC Chemical Biology Pub Date : 2025-08-25 DOI: 10.1039/d5cb00196j

Maho Miyamoto, Kosuke Saito, Hidetomo Yokoo, Yosuke Demizu

引用次数: 0

Fitness landscapes and thermodynamic approaches to development of nucleic acids enzymes: from classical methods to AI integration. 核酸酶发展的适应度景观和热力学方法：从经典方法到人工智能集成。

IF 3.1

RSC Chemical Biology Pub Date : 2025-08-21 DOI: 10.1039/d5cb00105f

Shuntaro Takahashi, Michiaki Hamada, Hisae Tateishi-Karimata, Naoki Sugimoto

{"title":"Fitness landscapes and thermodynamic approaches to development of nucleic acids enzymes: from classical methods to AI integration.","authors":"Shuntaro Takahashi, Michiaki Hamada, Hisae Tateishi-Karimata, Naoki Sugimoto","doi":"10.1039/d5cb00105f","DOIUrl":"10.1039/d5cb00105f","url":null,"abstract":"Nucleic acids (NA), namely DNA and RNA, dynamically fold and unfold to perform their functions in cells. Functional NAs include NA enzymes, such as ribozymes and DNAzymes. Their folding and target binding are governed by interactions between nucleobases, including base pairings, which follow thermodynamic principles. To elucidate biological mechanisms and enable diverse technical applications, it is essential to clarify the relationship between the primary sequence and the catalytic activity of NA enzymes. Unlike methods for predicting the stability of NA duplexes, which have been widely used for over half a century, predictive approaches for the catalytic activity of NA enzymes remain limited due to the low throughput of activity assays. However, recent advances in genome analysis and computational data science have significantly improved our understanding of the sequence-function relationship in NA enzymes. This article reviews the contributions of data-driven chemistry to understanding the reaction mechanisms of NA enzymes at the nucleotide level and predicting novel NA enzymes with catalytic activity from sequence information. Furthermore, we discuss potential databases for predicting NA enzyme activity under various solution conditions and their integration with artificial intelligence for future applications.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0