Nature chemical biology最新文献_第10页

Guiding generative AI 引导生成AI

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2025-02-25 DOI: 10.1038/s41589-025-01854-y

Russell Johnson

引用次数: 0

Turning down the heat 关掉暖气

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2025-02-25 DOI: 10.1038/s41589-025-01855-x

Grant Miura

引用次数: 0

Small molecules deliver big 小分子传递大分子

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2025-02-25 DOI: 10.1038/s41589-025-01856-w

Gene Chong

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Quantitative chemoproteomics reveals dopamine’s protective modification of Tau 定量化学蛋白质组学揭示了多巴胺对Tau蛋白的保护性修饰

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-02-20 DOI: 10.1038/s41589-025-01849-9

Qianwen Wang, Zhengtao Liu, Youjia Wang, Yuan Liu, Ying Chen, Shengnan Zhang, Wen Zeng, Dan Li, Fan Yang, Zhuohao He, Weidi Xiao, Cong Liu, Chu Wang

{"title":"Quantitative chemoproteomics reveals dopamine’s protective modification of Tau","authors":"Qianwen Wang, Zhengtao Liu, Youjia Wang, Yuan Liu, Ying Chen, Shengnan Zhang, Wen Zeng, Dan Li, Fan Yang, Zhuohao He, Weidi Xiao, Cong Liu, Chu Wang","doi":"10.1038/s41589-025-01849-9","DOIUrl":"https://doi.org/10.1038/s41589-025-01849-9","url":null,"abstract":"Dopamine (DA) is one of the most important neurotransmitters. Its oxidation leads to electrophilic quinone, which covalently modifies nucleophilic residues in proteins, resulting in ‘dopamination’. Individual dopaminated proteins have been studied, most of which were functionally damaged by dopamination. Here, we developed a quantitative chemoproteomic strategy to site-specifically measure proteins’ dopamination. More than 6,000 dopamination sites were quantified. Half-maximal inhibitory concentration values for 63 hypersensitive sites were measured. Among them, hypersensitive dopamination of two cysteines in microtubule-associated protein Tau was biochemically validated and functionally characterized to prevent Tau’s amyloid fibrillation and promote Tau-mediated assembly of microtubules. In addition, endogenous dopamination of Tau in mouse brain was detected through targeted mass spectrometry analysis. Our study not only provides a global portrait of dopamination but also discovers a protective role of DA in regulating the function of Tau, which will enhance our understanding of the physiological and pathological functions of DA in human brain.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"25 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Tracking E2-specific substrates 跟踪e2特异性底物

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-02-19 DOI: 10.1038/s41589-025-01848-w

Hannah B. L. Jones, Andreas Damianou, Benedikt M. Kessler

引用次数: 0

The small molecule Ebio3 inactivates the KCNQ2 channel without blocking the pore 小分子Ebio3使KCNQ2通道失活而不阻塞孔

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-02-19 DOI: 10.1038/s41589-025-01853-z

引用次数: 0

xrRNAs adopt a long-lived conformation that prevents exonuclease activity xrrna采用一种长寿命的构象来阻止核酸外切酶的活性

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-02-19 DOI: 10.1038/s41589-025-01844-0

引用次数: 0

Visualizing drug effects over time in live animals using optical pharmacodynamics 利用光学药效学在活体动物体内观察药物随时间的作用

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-02-14 DOI: 10.1038/s41589-025-01847-x

引用次数: 0

Lifetime of ground conformational state determines the activity of structured RNA 基构象态的寿命决定了结构RNA的活性

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-02-12 DOI: 10.1038/s41589-025-01843-1

Rhese D. Thompson, Derek L. Carbaugh, Joshua R. Nielsen, Ciara M. Witt, Edgar M. Faison, Rita M. Meganck, Atul Rangadurai, Bo Zhao, Jeffrey P. Bonin, Nathan I. Nicely, William F. Marzluff, Aaron T. Frank, Helen M. Lazear, Qi Zhang

{"title":"Lifetime of ground conformational state determines the activity of structured RNA","authors":"Rhese D. Thompson, Derek L. Carbaugh, Joshua R. Nielsen, Ciara M. Witt, Edgar M. Faison, Rita M. Meganck, Atul Rangadurai, Bo Zhao, Jeffrey P. Bonin, Nathan I. Nicely, William F. Marzluff, Aaron T. Frank, Helen M. Lazear, Qi Zhang","doi":"10.1038/s41589-025-01843-1","DOIUrl":"https://doi.org/10.1038/s41589-025-01843-1","url":null,"abstract":"Biomolecules continually sample alternative conformations. Consequently, even the most energetically favored ground conformational state has a finite lifetime. Here, we show that, in addition to the three-dimensional (3D) structure, the lifetime of a ground conformational state determines its biological activity. Using hydrogen–deuterium exchange nuclear magnetic resonance spectroscopy, we found that Zika virus exoribonuclease-resistant RNA (xrRNA) encodes a ground conformational state with a lifetime that is ~105–107 longer than that of canonical base pairs. Mutations that shorten the apparent lifetime of the ground state without affecting its 3D structure decreased exoribonuclease resistance in vitro and impaired virus replication in cells. Additionally, we observed this exceptionally long-lived ground state in xrRNAs from diverse infectious mosquito-borne flaviviruses. These results demonstrate the biological importance of the lifetime of a preorganized ground state and further suggest that elucidating the lifetimes of dominant 3D structures of biomolecules may be crucial for understanding their behaviors and functions.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"16 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Pharmacodynamics of Akt drugs revealed by a kinase-modulated bioluminescent indicator 激酶调节的生物发光指示剂揭示Akt药物的药效学

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-02-11 DOI: 10.1038/s41589-025-01846-y

Yan Wu, Chenzhou Hao, Chao Gao, Matt Hageman, Sungmoo Lee, Thomas A. Kirkland, Nathanael S. Gray, Yichi Su, Michael Z. Lin

{"title":"Pharmacodynamics of Akt drugs revealed by a kinase-modulated bioluminescent indicator","authors":"Yan Wu, Chenzhou Hao, Chao Gao, Matt Hageman, Sungmoo Lee, Thomas A. Kirkland, Nathanael S. Gray, Yichi Su, Michael Z. Lin","doi":"10.1038/s41589-025-01846-y","DOIUrl":"https://doi.org/10.1038/s41589-025-01846-y","url":null,"abstract":"Measuring pharmacodynamics (PD)—the biochemical effects of drug dosing—and correlating them with therapeutic efficacy in animal models is crucial for the development of effective drugs but traditional PD studies are labor and resource intensive. Here we developed a kinase-modulated bioluminescent indicator (KiMBI) for rapid, noninvasive PD assessment of Akt-targeted drugs, minimizing drug and animal use. Using KiMBI, we performed a structure–PD relationship analysis on the brain-active Akt inhibitor ipatasertib by generating and characterizing two novel analogs. One analog, ML-B01, successfully inhibited Akt in both the brain and the body. Interestingly, capivasertib, ipatasertib and ML-B01 all exhibited PD durations beyond their pharmacokinetic profiles. Furthermore, KiMBI revealed that the PD effects of an Akt-targeted proteolysis-targeting chimera degrader endured for over 3 days. Thus, bioluminescence imaging with Akt KiMBI provides a noninvasive and efficient method for in vivo visualization of the PD of Akt inhibitors and degraders.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"26 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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