Nature chemical biology最新文献_第3页

Reading sugars cell by cell 一个细胞一个细胞地读出糖。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-10-08 DOI: 10.1038/s41589-026-02342-7

Tongtong Wang, Peng Wu

引用次数: 0

High-resolution NMR spectroscopy of proteins in intact mitochondria 完整线粒体中蛋白质的高分辨率核磁共振波谱

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2026-10-07 DOI: 10.1038/s41589-026-02314-x

Zeting Zhang,Cai Zhang,Guohua Xu,Ruichen Du,Jinbo Yu,Xiaoli Liu,Zhaofei Chai,Qiong Wu,Ling Jiang,Maili Liu,Conggang Li

引用次数: 0

Retraction Note: α-Ketoglutarate dictates AMPK protein synthesis for energy sensing in human cancers 注：α-酮戊二酸决定AMPK蛋白的合成，用于人类癌症的能量感应

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-10-07 DOI: 10.1038/s41589-026-02346-3

Wen Mi, Yun Xue, Haohang Yan, Yurou Zhang, Xinlei Cai, Shuyuan Zhang, Ruiping He, Liucheng Li, Lingzhi Zhu, Xinyi Xia, Yifan Liang, Chongwen Cao, Yi Xu, Junfeng Bi, Guanlin Wang, Li Chen, Dan Ye, Fei Li, Ruobing Ren, Pingyu Liu, Hongbin Ji, Fuming Li

引用次数: 0

DHODH is the key target of the KDM4 inhibitor QC6352 in glioblastoma stem cells DHODH是KDM4抑制剂QC6352在胶质母细胞瘤干细胞中的关键靶点

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2026-10-06 DOI: 10.1038/s41589-026-02306-x

Jayden R. Sterling, Jacinda R. Holtsmark, George L. Joun, Matthew S. Graus, Tian Y. Du, Mani Kuchibhotla, Terrance G. Johns, Antoine deWeck, Lipin Loo, G. Gregory Neely, Karen Tran, Chloe Shard, Guillermo A. Gomez, Ashwini Patil, Diana D. Shi, Julie-Aurore Losman, Angus J. Saxton, Jennifer R. Baker, Zhihe Lei, Matthew T. O. Holland, Paul E. Brennan, Mathias Francois, Andreas Kraemer, Susanne Mueller, Yuchen Feng, Paul Workman, Lenka Munoz

{"title":"DHODH is the key target of the KDM4 inhibitor QC6352 in glioblastoma stem cells","authors":"Jayden R. Sterling, Jacinda R. Holtsmark, George L. Joun, Matthew S. Graus, Tian Y. Du, Mani Kuchibhotla, Terrance G. Johns, Antoine deWeck, Lipin Loo, G. Gregory Neely, Karen Tran, Chloe Shard, Guillermo A. Gomez, Ashwini Patil, Diana D. Shi, Julie-Aurore Losman, Angus J. Saxton, Jennifer R. Baker, Zhihe Lei, Matthew T. O. Holland, Paul E. Brennan, Mathias Francois, Andreas Kraemer, Susanne Mueller, Yuchen Feng, Paul Workman, Lenka Munoz","doi":"10.1038/s41589-026-02306-x","DOIUrl":"https://doi.org/10.1038/s41589-026-02306-x","url":null,"abstract":"Histone lysine demethylase 4 (KDM4) enzymes are frequently overexpressed in cancer and are considered to be promising therapeutic targets. QC6352, which is widely used as a best-in-class KDM4 chemical probe, shows potent antitumor activity across cancer models. Using comprehensive chemical biology approaches in glioblastoma models, we demonstrate that the efficacy of QC6352 and that of its clinical analog zavondemstat are independent of KDM4 inhibition. Instead, we identify dihydroorotate dehydrogenase (DHODH), a key enzyme in de novo pyrimidine biosynthesis, as the functional target driving their antiproliferative activity. Uridine supplementation and expression of an inhibitor-resistant DHODH mutant fully abrogate growth inhibition, whereas the orthogonal KDM4 inhibitor ML324, which lacks DHODH inhibition, fails to phenocopy QC6352. These findings establish QC6352 and zavondemstat as dual KDM4–DHODH inhibitors and identify DHODH inhibition as the dominant driver of their antiglioblastoma efficacy, as well as demonstrating the need for orthogonal chemical probes to accurately define drug mechanisms in cells.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"476 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087610","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

Context matters for drug targeting 背景对药物靶向很重要

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2026-10-06 DOI: 10.1038/s41589-026-02305-y

Mohammad Ali Mohammad Nezhady,Grace McKay-Corkum,Adam D. Durbin

引用次数: 0

Cell-cycle-driven noncanonical ubiquitination of METTL14 orchestrates RNA methylation 细胞周期驱动的METTL14非规范泛素化协调RNA甲基化

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2026-10-06 DOI: 10.1038/s41589-026-02328-5

Jie Cao, Xiner Ying, Lili Zhou, Qingyi Zhang, Chenyang Huang, Tong Dai, Xiao Shu, Minsong Gao, Yujie Mi, Xiaojin Wu, Fengqin Wang, Long Zhang, Fangfang Zhou, Xin-Hua Feng, Jianzhao Liu

{"title":"Cell-cycle-driven noncanonical ubiquitination of METTL14 orchestrates RNA methylation","authors":"Jie Cao, Xiner Ying, Lili Zhou, Qingyi Zhang, Chenyang Huang, Tong Dai, Xiao Shu, Minsong Gao, Yujie Mi, Xiaojin Wu, Fengqin Wang, Long Zhang, Fangfang Zhou, Xin-Hua Feng, Jianzhao Liu","doi":"10.1038/s41589-026-02328-5","DOIUrl":"https://doi.org/10.1038/s41589-026-02328-5","url":null,"abstract":"The precise temporal control of global mRNA methylation during the cell cycle is critical, yet the underlying mechanism remains unknown. Here we elucidate a noncanonical ubiquitination-mediated regulatory mechanism whereby RLIM deposits predominantly K27-linked ubiquitin (K27-Ub) on the m6A methyltransferase METTL14 in a cell-cycle-programmed manner. This modification modulates enzymatic activity by controlling METTL3–METTL14 complex assembly and RNA substrate engagement, independent of protein stability. We discover that transcriptome-wide mRNA m6A level, K27-Ub intensity on METTL14 and RLIM expression exhibit coordinated periodic oscillations during the cell cycle. Furthermore, this periodic regulation is mediated by CDK1/cyclin B1-directed phosphorylation of RLIM, triggering self-ubiquitination and proteasomal degradation. Functional investigations across multiple models, including human RLIM-knockout cells, myeloid-specific Rlim-knockout mice and participants with acute monocytic leukemia, demonstrate the pathophysiological importance of this previously unrecognized CDK1/cyclin B1–RLIM–METTL14–m6A axis. In summary, our findings identify a cell-cycle-coupled quality control mechanism for epitranscriptomic m6A regulation.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"1 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087614","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

Transcription remodeling and stalling by cisplatin-induced interstrand crosslinks 顺铂诱导的链间交联导致的转录重塑和停滞

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2026-10-02 DOI: 10.1038/s41589-026-02338-3

Liulian Zhu, Weiqi Zhao, Lei Ye, Yankai Liu, Wenjing Deng, Bingshuo Qian, Xin Yang, Jun Xu

{"title":"Transcription remodeling and stalling by cisplatin-induced interstrand crosslinks","authors":"Liulian Zhu, Weiqi Zhao, Lei Ye, Yankai Liu, Wenjing Deng, Bingshuo Qian, Xin Yang, Jun Xu","doi":"10.1038/s41589-026-02338-3","DOIUrl":"https://doi.org/10.1038/s41589-026-02338-3","url":null,"abstract":"Interstrand crosslinks (ICLs) block transcription by mechanisms that remain incompletely understood. Cisplatin induces ICLs that suppress transcription and contribute to its antitumor activity but these effects can be mitigated by transcription-coupled repair. Using reconstituted transcription systems and cryo-electron microscopy, we investigated how RNA polymerase II (Pol II) processes cisplatin-ICLs and captured eight sequential transcriptional states. Pol II unexpectedly remodels the crosslinked guanines into a novel conformation positioned above the bridge helix. This rearranged ICL prevents the damaged base from entering the active site and triggers Pol II backtracking following ATP misincorporation. Furthermore, Cockayne syndrome protein B, an ATP-dependent translocase that initiates transcription-coupled repair, neither promotes lesion bypass nor displaces stalled Pol II, thereby committing the lesion to transcription-coupled repair. These findings identify Pol II as a structural remodeler of cisplatin-ICLs and reveal how the remodeled lesion stalls transcription, providing insight into cellular responses to platinum-based chemotherapy.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"14 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087613","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

Advances in amidases and urethanases as depolymerization biocatalysts 氨基酶和脲酶解聚生物催化剂的研究进展

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-10-01 DOI: 10.1038/s41589-026-02325-8

Thomas Bayer, Hannes Meinert, Ren Wei, Uwe T. Bornscheuer

{"title":"Advances in amidases and urethanases as depolymerization biocatalysts","authors":"Thomas Bayer, Hannes Meinert, Ren Wei, Uwe T. Bornscheuer","doi":"10.1038/s41589-026-02325-8","DOIUrl":"10.1038/s41589-026-02325-8","url":null,"abstract":"Stable chemical bonds as well as noncovalent interactions define the properties of industrial chemicals and materials, including polyesters such as polyethylene terephthalate (PET), polyamides (nylons) and polyurethanes. The resistance of plastics to hydrolysis contributes to the global issues of waste accumulation and environmental pollution. Recently identified metagenomic enzymes act on highly stable ester, amide and carbamate bonds in small molecules as well as pretreated polymeric materials. However, depolymerization activities, particularly for nylons and polyurethanes, remain too low to facilitate the efficient treatment of plastic waste. This Perspective highlights the natural diversity of different hydrolase superfamilies suitable for deconstructing synthetic polymers and examines their catalytic features. We also discuss strategies for discovering biocatalysts and tailoring their properties by protein engineering—both assisted by bioinformatics and (ultra)high-throughput screening tools. The combination of these approaches and thorough process analyses will be required to advance hydrolase-based depolymerization of plastics beyond the current recycling schemes for PET. Increasingly diverse sequence repositories can be accessed through advanced bioinformatics tools. Complementary screening assays accelerate the identification and engineering of improved amidases and urethanases that act on highly stable bonds in plastics such as polyamides and polyurethanes.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"22 11","pages":"1720-1730"},"PeriodicalIF":15.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149092126","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

Multiomic proximity labeling in vivo by D-amino-acid-activated peroxidase reaction d-氨基酸活化过氧化物酶反应在体内的多组接近标记

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2026-09-30 DOI: 10.1038/s41589-026-02336-5

Jiapeng Liu, Jian Han, Yupu Wang, Mengjiao Song, Jianbei Zhu, Yu Liang, Fangyi Chen, Zhike Liu, Xinwen Yan, Ziyuan Wang, Weicheng Peng, Ruibo Tu, Zihan Zhang, Binglin Zhong, Hao Sun, Junyi Yin, Jingbo Chang, Yuying Long, Yinghui Men, Shang-Jui Tsai, Shanshan Wang, Teodorus Theo Susanto, Albert Qiang, Yong Chen, Weijun Pan, Yizhu Lin, Wei Wu, Yidong Shen, Jiefu Li, Yue Wan, Shuo Han

{"title":"Multiomic proximity labeling in vivo by D-amino-acid-activated peroxidase reaction","authors":"Jiapeng Liu, Jian Han, Yupu Wang, Mengjiao Song, Jianbei Zhu, Yu Liang, Fangyi Chen, Zhike Liu, Xinwen Yan, Ziyuan Wang, Weicheng Peng, Ruibo Tu, Zihan Zhang, Binglin Zhong, Hao Sun, Junyi Yin, Jingbo Chang, Yuying Long, Yinghui Men, Shang-Jui Tsai, Shanshan Wang, Teodorus Theo Susanto, Albert Qiang, Yong Chen, Weijun Pan, Yizhu Lin, Wei Wu, Yidong Shen, Jiefu Li, Yue Wan, Shuo Han","doi":"10.1038/s41589-026-02336-5","DOIUrl":"https://doi.org/10.1038/s41589-026-02336-5","url":null,"abstract":"Understanding the spatial organization of biomolecules in living organisms is a central but challenging goal in biology. Here, we introduce peroxidase reactions activated by D-amino acids (PRADA), which uses an engineered oxidase to convert nonproteinogenic D-amino acids into H2O2 for in situ activation of a genetically fused peroxidase. PRADA enables versatile proximity-based chemistries, including protein labeling, RNA labeling and functional polymer assembly, with minimal toxicity and background. We demonstrate that PRADA is broadly applicable inside living organisms, including flies, worms, fish and mice. By further leveraging the unique RNA reactivity of PRADA, we developed a mutational profiling sequencing strategy for spatiotemporally resolved mapping of RNA secondary structure. Application of this multifaceted PRADA platform in a mouse xenograft model offered insights into its mitochondrial proteome, transcriptome and RNA structurome, revealing RNA folding as a regulatory mechanism in mitochondrial gene expression. Collectively, PRADA holds promise to uncover the intricate organization of biomolecules in vivo.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"10 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087616","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

SRSF1 modulates the dark nucleolar cap pH to restore nucleolar integrity and function. SRSF1调节暗核仁帽pH值以恢复核仁完整性和功能。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-09-28 DOI: 10.1038/s41589-026-02316-9

Suibin Ma, Jierui Guo, Xiang Zhan, Fan Wu, Shuo Yang, Chaoqun Huang, Bo Wang

引用次数: 0