Nature chemical biology最新文献_第4页

Cytochrome P450 enzymes that form allenes and alkynes from prenyl groups. 细胞色素P450酶，由戊烯基形成烯和炔。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-09-28 DOI: 10.1038/s41589-026-02345-4

引用次数: 0

Control of ice thickness in cryo-EM via confinement 通过约束控制低温电子显微镜中冰的厚度

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2026-09-25 DOI: 10.1038/s41592-026-03244-1

Liming Zheng,Jiling Song,Xiaole Zhao,Jiacong Cao,Jie Xu,Zhengni Wang,Chenhui Zhang,Weiyu Sun,Buhang Chen,Xiaoyin Gao,Haonan Liu,Junhao Yang,Yu Xu,Luzhao Sun,Zhaohe Dai,Xiaoding Wei,Nan Liu,Hailin Peng,Hong-Wei Wang

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Halting translation by the letter with sequence-selective small molecules 停止用序列选择性小分子逐个字母的翻译

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2026-09-25 DOI: 10.1038/s41589-026-02318-7

Tilman Schneider-Poetsch,Minoru Yoshida,Takuhiro Ito,Shintaro Iwasaki

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Publisher Correction: Biosynthetic allene and alkyne formation by enzymatic prenyl demethylation. 出版者更正：生物性合成丙烯和炔的酶促去甲基化。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-09-24 DOI: 10.1038/s41589-026-02349-0

Mengting Liu, Masao Ohashi, Wenyu Han, Qingyang Zhou, Kendall N Houk, Yi Tang

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How natural enzymes use noncanonical redox cofactors. 天然酶如何利用非规范氧化还原辅助因子。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-09-22 DOI: 10.1038/s41589-026-02329-4

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Small-molecule inhibitors block NorA efflux by conformational trapping. 小分子抑制剂通过构象捕获阻止NorA外排。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-09-16 DOI: 10.1038/s41589-026-02319-6

Janine L Gray, Elizabeth V K Ledger, Tiffany Suwatthee, Thomas J Burden, Konstantina Arvaniti, Priyanka Mishra, Amber Sefton, Lydia E Papagora, Thomas B Clarke, Jennifer Riley, Erika G Pinto, Fraser Cunningham, Ian H Gilbert, David Gray, Da-Neng Wang, Kevin D Read, Thomas Lanyon-Hogg, Nathaniel J Traaseth, Andrew M Edwards, Edward W Tate

{"title":"Small-molecule inhibitors block NorA efflux by conformational trapping.","authors":"Janine L Gray, Elizabeth V K Ledger, Tiffany Suwatthee, Thomas J Burden, Konstantina Arvaniti, Priyanka Mishra, Amber Sefton, Lydia E Papagora, Thomas B Clarke, Jennifer Riley, Erika G Pinto, Fraser Cunningham, Ian H Gilbert, David Gray, Da-Neng Wang, Kevin D Read, Thomas Lanyon-Hogg, Nathaniel J Traaseth, Andrew M Edwards, Edward W Tate","doi":"10.1038/s41589-026-02319-6","DOIUrl":"https://doi.org/10.1038/s41589-026-02319-6","url":null,"abstract":"Multidrug efflux pumps are major drivers of antibiotic resistance, yet progress in understanding and inhibiting these transporters has been limited by a lack of selective chemical probes and inhibitor-bound structures. Here we report IMP-2380, a potent and selective chemical probe targeting the clinically important Staphylococcus aureus efflux pump NorA. A phenotypic high-throughput screen monitoring suppression of the ciprofloxacin-induced SOS DNA damage response identified a chemical series that selectively inhibits NorA and was optimized to yield IMP-2380. The probe restores ciprofloxacin susceptibility in methicillin-resistant S. aureus, delivering low-nanomolar potentiation in vitro and robust efficacy in an in vivo infection model. Cryo-electron microscopy at 2.52-Å resolution revealed the structure of NorA bound to a small-molecule inhibitor. IMP-2380 binds an 'outward-open' transporter conformation, occluding the cytosolic substrate-binding cavity and preventing antibiotic efflux. IMP-2380 provides a high-quality probe for dissecting multidrug efflux and establishes a structural framework for restoring antibiotic efficacy through efflux pump inhibition.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":" ","pages":""},"PeriodicalIF":15.8,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982578","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

Biosynthetic allene and alkyne formation by enzymatic prenyl demethylation. 酶法丙烯基去甲基化合成丙烯和炔。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-09-15 DOI: 10.1038/s41589-026-02323-w

Mengting Liu, Masao Ohashi, Wenyu Han, Qingyang Zhou, Kendall N Houk, Yi Tang

{"title":"Biosynthetic allene and alkyne formation by enzymatic prenyl demethylation.","authors":"Mengting Liu, Masao Ohashi, Wenyu Han, Qingyang Zhou, Kendall N Houk, Yi Tang","doi":"10.1038/s41589-026-02323-w","DOIUrl":"10.1038/s41589-026-02323-w","url":null,"abstract":"Allenes and alkynes are versatile functional groups in chemical biology and drug discovery. However, how nature biosynthetically installs them in natural products, especially allenes, remains poorly understood. Here we uncovered that allenes and alkynes can be formed enzymatically through oxidative C(sp2)-demethylation of the common five-carbon prenyl group. Two fungal cytochrome P450 monooxygenases, PpnB and NseB, from the penipratynolene and sinuxylamide biosynthetic pathways, respectively, were shown to catalyze oxidative removal of a C(sp2)-methyl group in O-prenyl L-tyrosine to afford O-homoallenyl L-tyrosine and O-but-2-ynyl L-tyrosine, respectively. Combining density functional theory calculations and biochemical assays with isotopically labeled substrates, a mechanism involving selective C-C bond cleavage followed by product-determining hydrogen atom abstraction is presented. An additional P450 enzyme from the penipratynolene pathway, PpnD, acts as an oxidative isomerase that converts the four-carbon terminal allene into a terminal alkyne. This sophisticated enzymatic editing strategy to install allene and alkyne expands the catalytic repertoire of P450 enzymes.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":" ","pages":""},"PeriodicalIF":15.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977293","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

Multiplexed imaging 多路复用成像。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-09-14 DOI: 10.1038/s41589-026-02333-8

Huijuan Guo

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Decoding the recoding 解码重新编码。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-09-14 DOI: 10.1038/s41589-026-02330-x

Grant Miura

引用次数: 0

The making of mucus 粘液的产生