Nature Chemical Biology
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A scientific journal devoted to publishing the most compelling research, opinion and analysis at the intersection of chemistry and biology.
High-resolution NMR spectroscopy of proteins in intact mitochondria www.nature.com/articles/s41...
High-resolution NMR spectroscopy of proteins in intact mitochondria - Nature Chemical Biology
An approach has been developed for NMR observation of proteins within intact mitochondria through delivery of proteins directly into isolated mitochondria via electroporation. This method offers a fra...
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QC6352, originally developed as a KDM4 inhibitor, exerts its anticancer activity in glioblastoma models primarily through inhibition of DHODH, a key enzyme in de novo pyrimidine biosynthesis www.nature.com/articles/s41...
DHODH is the key target of the KDM4 inhibitor QC6352 in glioblastoma stem cells - Nature Chemical Biology
QC6352, originally developed as a KDM4 inhibitor, exerts its anticancer activity in glioblastoma models primarily through inhibition of dihydroorotate dehydrogenase, a key enzyme in de novo pyrimidine...
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Cell-cycle-driven noncanonical ubiquitination of METTL14 orchestrates RNA methylation www.nature.com/articles/s41...
Cell-cycle-driven noncanonical ubiquitination of METTL14 orchestrates RNA methylation - Nature Chemical Biology
Cao, Ying, Zhou, Zhang and colleagues identified a CDK1/cyclin B1–RLIM–METTL14 axis that couples the cell cycle to mRNA m6A dynamics through periodic RLIM-mediated K27-linked ubiquitination on methylt...
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Cryo-EM structures of RNA polymerase II (Pol II) with cisplatin-induced DNA interstrand crosslinks (ICLs) reveal how Pol II remodels cisplatin-ICLs, stalls transcription, and commits lesions to transcription-coupled repair www.nature.com/articles/s41...
Transcription remodeling and stalling by cisplatin-induced interstrand crosslinks - Nature Chemical Biology
By solving the cryo-electron microscopy structures of cisplatin-induced DNA interstrand crosslinks (ICLs) in complex with RNA polymerase II, Zhu, Zhao and colleagues reveal how RNA polymerase II remod...
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A nontoxic proximity labeling method generating H2O2 in situ from D-amino acids enables protein and RNA proximity labeling and mapping RNA structural changes in vitro and in vivo www.nature.com/articles/s41...
Multiomic proximity labeling in vivo by D-amino-acid-activated peroxidase reaction - Nature Chemical Biology
A nontoxic proximity labeling approach is developed using an engineered D-amino acid oxidase and APEX2 fusion to generate H2O2 in situ from D-amino acids. It is applied in vivo in Caenorhabditis elega...
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SRSF1 modulates the dark nucleolar cap pH to restore nucleolar integrity and function www.nature.com/articles/s41...
SRSF1 modulates the dark nucleolar cap pH to restore nucleolar integrity and function - Nature Chemical Biology
This study finds that SRSF1, a nuclear speckle-resident splicing factor, modulates the pH microenvironment in the dark nucleolar caps through its intrinsic positive charge, thereby ensuring nucleolar ...
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A new Review highlights the mechanisms of molecules that disrupt translation in an amino acid or mRNA sequence-dependent manner www.nature.com/articles/s41...
Halting translation by the letter with sequence-selective small molecules - Nature Chemical Biology
Small-molecule modulators of protein synthesis are invaluable tools for dissecting the translation apparatus. This Review summarizes the mechanisms of molecules that disrupt translation in an amino ac...
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Our October issue is live! www.nature.com/nchembio/vol... Inspired by the phases of the moon, the cover artwork uses light and darkness to depict pharmacological control of chimeric antigen receptor (CAR) T cells
Allenes and alkynes can be biosynthesized via oxidative C(sp2)-demethylation of a prenyl group by fungal cytochrome P450s, expanding the catalytic repertoire of P450 enzymes www.nature.com/articles/s41...
Biosynthetic allene and alkyne formation by enzymatic prenyl demethylation - Nature Chemical Biology
Allenes and alkynes are important functional groups in chemical biology, yet their biosynthesis is poorly understood. Now, Liu et al. reveal that they form via oxidative C(sp2)-demethylation of the pr...
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Happy New Paper Day! We're excited to share this @natchembio.nature.com on #SmallMoleculeInhibitors of NorA, an efflux pump that is an important mediator of #antibioticresistance in #MRSA. It pumps antibiotics out , lowering their concentration in the cell. doi.org/10.1038/s415...
Small-molecule inhibitors block NorA efflux by conformational trapping - Nature Chemical Biology
Multidrug efflux pumps expel antibiotics, contributing to antibiotic resistance. Now, high-throughput screening and structural characterization reveal an inhibitor of Staphylococcus aureus efflux pump...
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AvaS is a pyridoxal-phosphate-dependent RNA-modifying enzyme, producing the tRNA modification ava2C from k2C in bacteria and plants and linking RNA chemistry to translational regulation of metabolic stress responses www.nature.com/articles/s41...
Pyridoxal-phosphate-dependent biosynthesis of aminovaleramide by AvaS in tRNA - Nature Chemical Biology
Sun, Wu et al. identify AvaS as a pyridoxal-phosphate-dependent RNA-modifying enzyme, producing the tRNA modification ava2C from k2C in bacteria and plants and linking RNA chemistry to translational r...
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A sequence motif enables widespread use of noncanonical redox cofactors in natural enzymes www.nature.com/articles/s41...
A sequence motif enables widespread use of noncanonical redox cofactors in natural enzymes - Nature Chemical Biology
Noncanonical redox cofactors (NRCs) are promising alternatives to nicotinamide adenine dinucleotide (phosphate) (NAD(P)+) for biomanufacturing because of expanded capabilities and lower cost; however,...
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Plasma membrane order maps functional diversity in immune cells www.nature.com/articles/s41...
Plasma membrane order maps functional diversity in immune cells - Nature Chemical Biology
Cells undergo membrane remodeling in response to the environment to perform specific functions. Now, a cytometry-based method with immune cell biomarker analysis captures variations in plasma membrane...
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Chemogenomic maps reveal a PRDX1-dependent iron-damage axis in the DNA damage response www.nature.com/articles/s41...
Chemogenomic maps reveal a PRDX1-dependent iron–damage axis in the DNA damage response - Nature Chemical Biology
Large-scale CRISPR dependency mapping reveals 1,000+ genes that modify cellular outcomes to DNA damage response drugs. Loss of PRDX1, acting through a PAX7–MRGBP–IREB2 pathway, broadly sensitized cell...
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Macrophages transfer functional proteins to their surface during live-cell uptake www.nature.com/articles/s41...
Macrophages transfer functional proteins to their surface during live-cell uptake - Nature Chemical Biology
Macrophages acquire intact surface proteins from cancer cells during live-cell uptake, with these proteins remaining active, revealing a transcriptionally silent process where macrophages can reengine...
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Directed evolution of Lantern enables rapid RNA and protein proximity labeling www.nature.com/articles/s41...
Directed evolution of Lantern enables rapid RNA and protein proximity labeling - Nature Chemical Biology
Fang, Ren, Zheng, Wang et al. developed Lantern, a variant of miniSOG, through directed evolution for subcellular transcriptomes and proteomes analyses inside living cells, enabling findings that RNA ...
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Mechanism of the Mtb DprE1-DprE2 epimerase complex involved in cell wall synthesis and inhibition by anti-tubercular drugs www.nature.com/articles/s41...
Mechanism of the M. tuberculosis DprE1–DprE2 epimerase complex and inhibition by anti-tubercular drugs - Nature Chemical Biology
Pretomanid and delamanid are prodrugs reported to target the decaprenylphosphoribose-2′-reductase DprE2, while the noncovalent inhibitor quabodepistat has been reported to target the decaprenylphospho...
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α2,3- or α2,6-sialoglycan linkage-specific barcoding is developed and, combined with scRNA-seq, reveals differential regulation and function of α2,3- and α2,6-sialylation in subpopulations of tumor-infiltrating immune cells www.nature.com/articles/s41...
α2,6-Sialoglycan-regulated antitumor immunity of tumor-infiltrating CD8+ T cells - Nature Chemical Biology
Although hypersialylation on cancer cells and its roles in immune evasion and metastasis are well known, the functional roles of cell-surface sialylation on tumor-infiltrating immune cells (TIICs) are...
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An enantioselective covalent inhibitor of BAX constrains BAX conformation and suppresses pathological cell death in mouse liver and human motor neurons www.nature.com/articles/s41...
An enantioselective covalent inhibitor of BAX confers cytoprotection in vivo - Nature Chemical Biology
An enantioselective covalent inhibitor was developed that restrains BAX, protecting mouse liver and human motor neurons from injury and establishing covalent BAX inhibition as a promising strategy to ...
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A new Perspective by Changhao He and Kevan Shokat on the adaptive mechanisms and emerging chancer therapeutics for CDK2 inhibitors www.nature.com/articles/s41...
Our September issue is live! www.nature.com/nchembio/vol... The cover image depicts the localization of MESH1 (green) to the Golgi (red and yellow). MESH1 is identified to regulate the availability of the universal biological sulfate donor PAPS.
Targeted brain delivery of biologics through conjugation of a small molecule targeting a brain-enriched receptor, carbonic anhydrase IV (CA-IV) www.nature.com/articles/s41...
CA-IV-directed small-molecule shuttle enables targeted brain delivery of biologics - Nature Chemical Biology
Existing receptor targets to direct delivery of biologics across the blood−brain barrier are ubiquitously expressed in the central nervous system (CNS) and peripheral tissues. Now, carbonic anhydrase ...
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A new paper reveals the mechanisms of topogenic sequence recognition in mitochondrial inner membrane complexes TIM23 and TIM22 www.nature.com/articles/s41...
Topogenic sequence recognition at TIM complexes revealed by a stendomycin-bound structure - Nature Chemical Biology
The mitochondrial inner membrane complexes TIM23 and TIM22 mediate distinct protein topogenesis functions in polypeptide import. The authors reveal their mechanistic overlap in topogenic sequence reco...
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A new Comment discusses the advances and potential of agentic AI systems in drug discovery www.nature.com/articles/s41...
Entering the agentic era of AI in drug discovery - Nature Chemical Biology
Agentic AI systems are reshaping drug discovery, and the convergence of agentic AI with laboratory automation is enabling the design of self-driving laboratories that transform the design–make–test–an...
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📢 Thrilled to share our new publication in @natchembio.nature.com, led by our former graduate student Ryan Weeks! In this work, we develop HaloRasAR, a chemigenetic biosensor capable of detecting endogenous Ras by fluorogenic increase in far-red fluorescence. Find out more in the paper!
A chemigenetic endogenous Ras activity biosensor for live-cell pharmacology - Nature Chemical Biology
Here the authors present a biosensor for measuring endogenous Ras in live cells, based on HaloTag and the fluorogenic JF635 dye, and they use it to report location-specific inhibition profiles of dist...
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ryan weeks@ryanweeeeks.bsky.social · 2mo agoReally excited to share the publication of my PhD work in the Jin Zhang lab at UCSD! You can find it here in Nature Chemical Biology. www.nature.com/articles/s41...
Biological circuit boards are engineered that compute functions based on the spatial arrangement of different bacterial strains printed on a surface www.nature.com/articles/s41...
Living circuit boards built by printing bacterial transistors - Nature Chemical Biology
Electronic circuit boards carry out different operations on the basis of the configuration of their components. Now, equivalent biological circuits are engineered that compute functions on the basis o...
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Photoproximity labeling of c-Myc reveals SLK as a cancer-specific co-regulator www.nature.com/articles/s41...
Photoproximity labeling of c-Myc reveals SLK as a cancer-specific co-regulator - Nature Chemical Biology
A photoproximity-labeling approach maps cancer-specific partners of the c-Myc oncoprotein, revealing that the kinase SLK binds and stabilizes c-Myc, drives tumor growth and offers a new strategy to ta...
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Bronsted-basic small molecules activate GTP hydrolysis in KRAS-Q61 mutants www.nature.com/articles/s41...
Brønsted-basic small molecules activate GTP hydrolysis in KRAS-Q61 mutants - Nature Chemical Biology
Through chemical complementation, Brønsted-basic small molecules rescue the loss of the catalytic glutamine side chain in KRAS-Q61X mutants, accelerating GTP hydrolysis up to 20-fold.
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A chemical screen identifies a PRC2-AR-ETV1-PPP axis that regulates pancreatic β cell identity features in α cells. An intermediate PPP metabolite induces metabolic reprogramming to stimulate β cell regeneration www.nature.com/articles/s41...
Metabolic reprogramming drives pancreatic β cell neogenesis from α cells - Nature Chemical Biology
A chemical screen identified a PRC2–AR–ETV1–PPP axis that regulates β cell identity features in α cells. An intermediate PPP metabolite, methyl esterified 6-phosphogluconate, induced metabolic reprogr...
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A covalent PFKL activator suppresses tumor growth www.nature.com/articles/s41...
A covalent PFKL activator suppresses tumor growth - Nature Chemical Biology
An electrophile–drug conjugate covalently activates PFKL through K677 engagement and releases a selective CPT2-targeting payload. This strategy exploits metabolic vulnerabilities to suppress tumor gro...
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