Keth-seq for transcriptome-wide RNA structure mapping

Posted on Feb 3rd, 2020 - By Xiaocheng Weng

Nature Chemical Biology, Published online: 03 February 2020; doi:10.1038/s41589-019-0459-3The authors designed a chemical probe, azido-kethoxal, to specifically label guanosine in single-strand RNAs in live cells that could be used to determine transcriptome-wide RNA secondary…

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Stress-tolerant non-conventional microbes enable next-generation chemical biosynthesis

Posted on Jan 23rd, 2020 - By Sarah Thorwall

Nature Chemical Biology, Published online: 23 January 2020; doi:10.1038/s41589-019-0452-xThe native stress-tolerant phenotypes of various non-conventional microbes have the potential to enable more efficient bioprocessing for chemical production, addressing certain design challenges encountered when using model production…

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Spores hit the spot

Posted on Jan 23rd, 2020 - By Chao Zhong

Nature Chemical Biology, Published online: 23 January 2020; doi:10.1038/s41589-019-0451-yEngineered living materials (ELMs) with the qualities of both programmable functionalities and environmental tolerance are rare. 3D printing of bacterial spores into resilient living materials provides a viable route to fabricate ELMs that integrate these material…

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Lipid hijacking

Posted on Jan 23rd, 2020 - By Mirella Bucci

Nature Chemical Biology, Published online: 23 January 2020; doi:10.1038/s41589-020-0465-5Lipid…

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Noise reduction

Posted on Jan 23rd, 2020 - By Grant Miura

Nature Chemical Biology, Published online: 23 January 2020; doi:10.1038/s41589-020-0464-6Noise…

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A dual function PUS enzyme

Posted on Jan 23rd, 2020 - By Wen Zhang

Nature Chemical Biology, Published online: 23 January 2020; doi:10.1038/s41589-019-0450-zThe traditional function of pseudouridine synthases is to convert uridine residues in RNA to pseudouridines. A study reveals a new function for the human PUS10 protein, which enhances micro-RNA maturation in addition to tRNA…

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New beginnings

Posted on Jan 23rd, 2020 - By Yiyun Song

Nature Chemical Biology, Published online: 23 January 2020; doi:10.1038/s41589-020-0466-4New…

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Spying on the microbiome

Posted on Jan 23rd, 2020 - By Caitlin Deane

Nature Chemical Biology, Published online: 23 January 2020; doi:10.1038/s41589-020-0463-7Spying on the…

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Chris Dobson (1949–2019)

Posted on Jan 23rd, 2020 - By Tuomas P. J. Knowles

Nature Chemical Biology, Published online: 23 January 2020; doi:10.1038/s41589-019-0456-6Chris Dobson passed away on September 8th, leaving a wide-reaching legacy. He is best known for revealing the generality of the phenomenon of protein misfolding and aggregation and has provided inspiration for generations of…

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Structural equilibrium underlying ligand-dependent activation of β<sub>2</sub>-adrenoreceptor

Posted on Jan 20th, 2020 - By Shunsuke Imai

Nature Chemical Biology, Published online: 20 January 2020; doi:10.1038/s41589-019-0457-5NMR structural analysis of an active state of the β2-adrenergic receptor defines a unique orientation for the intracellular half of TM6, responsible for G-protein binding, including an equilibrium among three conformations of a key…

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Biased modulators of NMDA receptors control channel opening and ion selectivity

Posted on Jan 20th, 2020 - By Riley E. Perszyk

Nature Chemical Biology, Published online: 20 January 2020; doi:10.1038/s41589-019-0449-5A series of positive allosteric modulators of NMDA receptors that can increase agonist potency, increase channel-open probability, and slow receptor deactivation can also decrease single-channel conductance and decrease calcium…

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Molecular basis for receptor tyrosine kinase A-loop tyrosine transphosphorylation

Posted on Jan 20th, 2020 - By Lingfeng Chen

Nature Chemical Biology, Published online: 20 January 2020; doi:10.1038/s41589-019-0455-7X-ray crystallography, solution NMR and biochemical and cell-based analyses reveal a model where catalytically repressed receptor tyrosine kinases accomplish activation loop (A-loop) tyrosine…

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Author Correction: Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex

Posted on Jan 15th, 2020 - By Dirksen E. Bussiere

Nature Chemical Biology, Published online: 15 January 2020; doi:10.1038/s41589-020-0471-7Author Correction: Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase…

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Publisher Correction: An efficient gene knock-in strategy using 5′-modified double-stranded DNA donors with short homology arms

Posted on Jan 15th, 2020 - By Yi Yu

Nature Chemical Biology, Published online: 15 January 2020; doi:10.1038/s41589-020-0470-8Publisher Correction: An efficient gene knock-in strategy using 5′-modified double-stranded DNA donors with short homology…

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Molecular basis for fibroblast growth factor 23 <i>O</i>-glycosylation by GalNAc-T3

Posted on Jan 13th, 2020 - By Matilde de las Rivas

Nature Chemical Biology, Published online: 13 January 2020; doi:10.1038/s41589-019-0444-xPolypeptide GalNAc-transferase T3 catalyzes the specific glycosylation of threonine-178 of fibroblast growth factor 23, and structural insights reveal a unique lectin-based mechanism of substrate…

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Reprogramming fatty acyl specificity of lipid kinases via C1 domain engineering

Posted on Jan 13th, 2020 - By Timothy B. Ware

Nature Chemical Biology, Published online: 13 January 2020; doi:10.1038/s41589-019-0445-9A chemoproteomics and protein engineering strategy to investigate metabolic activity of lipid kinases led to assignment of a key role for atypical C1 domains in directing fatty acyl specificity of diacylglycerol kinase function in live…

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A fungal family of lytic polysaccharide monooxygenase-like copper proteins

Posted on Jan 13th, 2020 - By Aurore Labourel

Nature Chemical Biology, Published online: 13 January 2020; doi:10.1038/s41589-019-0438-8The X325 protein family is highly similar to lytic polysaccharide monooxygenases (LPMOs) in regulation, structure and copper coordination by a histidine brace, yet lacks LPMO activity and suggests the evolution of an alternative function in…

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Rewiring E2 enzymes

Posted on Jan 13th, 2020 - By Koichi Sato

Nature Chemical Biology, Published online: 13 January 2020; doi:10.1038/s41589-019-0454-8The site-specific monoubiquitination of FANCD2 is crucial for the Fanconi anemia DNA repair pathway and tumor suppression. This modification is mediated by the E2 enzyme UBE2T and the E3 ligase FANCL through a novel allosteric…

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Lipid droplets can promote drug accumulation and activation

Posted on Jan 13th, 2020 - By Ramin Dubey

Nature Chemical Biology, Published online: 13 January 2020; doi:10.1038/s41589-019-0447-7Lasonolide A is hydrolyzed into a cytotoxic metabolite by a lipid droplet-associated orphan serine hydrolase, showing that lipid droplets can promote drug toxicity by both accumulating and metabolizing drugs in…

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A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis

Posted on Jan 13th, 2020 - By Sarela Garcia-Santamarina

Nature Chemical Biology, Published online: 13 January 2020; doi:10.1038/s41589-019-0437-9In the fungal pathogen Cryptococcus neoformans, Bim1 is a copper-binding lytic polysaccharide monooxygenase-like protein that participates in copper uptake in concert with the Ctr1 importer to drive virulence mechanisms during fungal…

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Chain alignment of collagen I deciphered using computationally designed heterotrimers

Posted on Jan 6th, 2020 - By Abhishek A. Jalan

Nature Chemical Biology, Published online: 06 January 2020; doi:10.1038/s41589-019-0435-yDesigned heterotrimers of collagen I, locked in three possible chain registers, enable structural and functional characterization of each permutation, leading to identification of the AAB heterotrimer as the most active and therefore likely to occur…

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A tunable orthogonal coiled-coil interaction toolbox for engineering mammalian cells

Posted on Jan 6th, 2020 - By Tina Lebar

Nature Chemical Biology, Published online: 06 January 2020; doi:10.1038/s41589-019-0443-yA set of orthogonal coiled-coil peptide heterodimers were developed to enable control of protein localization as well as transcriptional regulation by enhancing effector recruitment to TALE and CRISPR–dCas9 systems in mammalian cells and in…

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Publisher Correction: The chemical basis of ferroptosis

Posted on Jan 2nd, 2020 - By Marcus Conrad

Nature Chemical Biology, Published online: 02 January 2020; doi:10.1038/s41589-019-0434-zPublisher Correction: The chemical basis of…

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Allosteric mechanism for site-specific ubiquitination of FANCD2

Posted on Dec 23rd, 2019 - By Viduth K. Chaugule

Nature Chemical Biology, Published online: 23 December 2019; doi:10.1038/s41589-019-0426-zUBE2T adopts an allosteric activation mechanism to mediate site-specific ubiquitination of Fanconi anemia complex. Interaction with FANCL induces a cascade of conformational changes of UBE2T and leads to exposure of substrate-binding…

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Regulation of PTP1B activation through disruption of redox-complex formation

Posted on Dec 23rd, 2019 - By Avinash D. Londhe

Nature Chemical Biology, Published online: 23 December 2019; doi:10.1038/s41589-019-0433-0A transient interaction between 14-3-3ζ and a loop of PTP1B is detected following PTP1B inactivation by reversible…

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Dynamics of transcription–translation coordination tune bacterial indole signaling

Posted on Dec 23rd, 2019 - By Tianmin Wang

Nature Chemical Biology, Published online: 23 December 2019; doi:10.1038/s41589-019-0430-3The authors utilize fluorescence-activated cell sorting coupled with next-generation sequencing, as well as dynamic modeling, to study the molecular mechanism underlying indole signaling and reveal different roles of the two ends of tnaC in coordinating transcription and…

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An efficient gene knock-in strategy using 5′-modified double-stranded DNA donors with short homology arms

Posted on Dec 23rd, 2019 - By Yi Yu

Nature Chemical Biology, Published online: 23 December 2019; doi:10.1038/s41589-019-0432-1A simple and effective strategy is introduced to increase CRISPR–Cas9-mediated gene knock-in rates by using 5′-modified double-stranded DNA donors with short homology…

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Trashing transcription

Posted on Dec 16th, 2019 - By Yiyun Song

Nature Chemical Biology, Published online: 16 December 2019; doi:10.1038/s41589-019-0442-zTrashing…

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Dynamics of the context-specific translation arrest by chloramphenicol and linezolid

Posted on Dec 16th, 2019 - By Junhong Choi

Nature Chemical Biology, Published online: 16 December 2019; doi:10.1038/s41589-019-0423-2Single-molecule FRET technologies reveal the mechanism of sequence-specific translational inhibition induced by two antibiotics, chloramphenicol and linezolid, where aminoacyl-tRNA was repeatedly rejected from the A-site and failed to form a peptide…

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Tailor-made GPCRs

Posted on Dec 16th, 2019 - By R. Scott Prosser

Nature Chemical Biology, Published online: 16 December 2019; doi:10.1038/s41589-019-0427-yAn in silico directed evolution approach using first principles of allostery predicts the effects of protein sequence and structure variation on constitutive activity and ligand response in…

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Peptides skip a beat

Posted on Dec 16th, 2019 - By Mirella Bucci

Nature Chemical Biology, Published online: 16 December 2019; doi:10.1038/s41589-019-0441-0Peptides skip a…

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Mammalian signaling circuits from bacterial parts

Posted on Dec 16th, 2019 - By Xiaoyu Yang

Nature Chemical Biology, Published online: 16 December 2019; doi:10.1038/s41589-019-0436-xThe ability to engineer synthetic signaling networks has proven challenging for synthetic biology. A breakthrough design strategy shows that bacterial two-component-system-derived parts can be grafted into mammalian cells to create programmable phosphorylation…

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Engineering yeast phospholipid metabolism for de novo oleoylethanolamide production

Posted on Dec 16th, 2019 - By Yi Liu

Nature Chemical Biology, Published online: 16 December 2019; doi:10.1038/s41589-019-0431-2A combinatorial engineering strategy encompassing pathway regulation, heterologous enzymes and subcellular trafficking enables repurposing of the phospholipid biosynthetic pathway in Saccharomyces cerevisiae for the production of…

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Forging a new connection

Posted on Dec 16th, 2019 - By Caitlin Deane

Nature Chemical Biology, Published online: 16 December 2019; doi:10.1038/s41589-019-0439-7Forging a new…

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Artificial signaling in mammalian cells enabled by prokaryotic two-component system

Posted on Dec 16th, 2019 - By Alain Mazé

Nature Chemical Biology, Published online: 16 December 2019; doi:10.1038/s41589-019-0429-9Bacterial two-component signaling machinery has been reprogrammed for orthogonal signaling in mammalian cells that is triggered by small-molecule-mediated dimerization or ligand-induced GPCR/β-arrestin…

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CPSF3-dependent pre-mRNA processing as a druggable node in AML and Ewing’s sarcoma

Posted on Dec 9th, 2019 - By Nathan T. Ross

Nature Chemical Biology, Published online: 09 December 2019; doi:10.1038/s41589-019-0424-1The RNA endonuclease CPSF3 was identified as the cellular efficacy target of the small molecule JTE-607, revealing pre-mRNA processing as a vulnerability in cancers such as Ewing’s sarcoma that are characterized by aberrant…

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Molecular glue concept solidifies

Posted on Dec 9th, 2019 - By Kheewoong Baek

Nature Chemical Biology, Published online: 09 December 2019; doi:10.1038/s41589-019-0414-3Molecular-glue-mediated proximity-induced degradation now allows unprecedented therapeutic targeting of previously undruggable proteins. Structures showing how aryl-sulfonamides mediate recruitment of the splicing factor RBM39 to the E3 CRL4DCAF15 broaden the mechanistic principles by which molecular glues target…

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Discovery of a first-in-class EZH2 selective degrader

Posted on Dec 9th, 2019 - By Anqi Ma

Nature Chemical Biology, Published online: 09 December 2019; doi:10.1038/s41589-019-0421-4A hydrophobic tagging method is used to develop a selective degrader for the chromatin regulator EZH2, which inhibits proliferation of triple-negative breast cancer cell lines in vitro and in…

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Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex

Posted on Dec 9th, 2019 - By Dirksen E. Bussiere

Nature Chemical Biology, Published online: 09 December 2019; doi:10.1038/s41589-019-0411-6The crystal and cryo-electron microscopy structure analysis of the DCAF15–DDB1–DDA1–indisulam–RBM39 complex revealed the detailed mechanism of action of indisulam-induced RBM39 degradation and defined an α-helical degron motif in…

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Processing for destruction

Posted on Dec 9th, 2019 - By Michael A. Erb

Nature Chemical Biology, Published online: 09 December 2019; doi:10.1038/s41589-019-0428-xPhenotypic screening is an engine of discovery for bioactive small molecules and can unravel novel mechanisms and pathways controlling cellular physiology. A recent study reveals the CPSF complex as a pharmacologically tractable target of JTE-607 and context-specific cancer…

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Differential roles of human PUS10 in miRNA processing and tRNA pseudouridylation

Posted on Dec 9th, 2019 - By Jinghui Song

Nature Chemical Biology, Published online: 09 December 2019; doi:10.1038/s41589-019-0420-5PUS10 exhibits two different functions: one is to promote miRNA biogenesis in a catalytically independent manner; the other is to install pseudouridine modification in tRNAs in a catalytically dependent…

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A basic motif anchoring ISWI to nucleosome acidic patch regulates nucleosome spacing

Posted on Dec 9th, 2019 - By Hai T. Dao

Nature Chemical Biology, Published online: 09 December 2019; doi:10.1038/s41589-019-0413-4A photocrosslinking-based nucleosome profiling approach is used to identify a conserved basic motif in the ISWI remodeler SNF2h that anchors it to the acidic patch of nucleosome and enables nucleosome sliding…

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Accurate annotation of human protein-coding small open reading frames

Posted on Dec 9th, 2019 - By Thomas F. Martinez

Nature Chemical Biology, Published online: 09 December 2019; doi:10.1038/s41589-019-0425-0An improved workflow combining de novo transcriptome assembly and Ribo-seq validated by cellular antigen display is developed to maximize small peptide discovery, leading to identification of thousands of unannotated protein-coding…

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Computational design of G Protein-Coupled Receptor allosteric signal transductions

Posted on Dec 2nd, 2019 - By Kuang-Yui Michael Chen

Nature Chemical Biology, Published online: 02 December 2019; doi:10.1038/s41589-019-0407-2A computational approach for designing GPCRs with new signaling functions including allosteric signaling properties yielded D2 receptor variants with predictable G-protein signaling responses, some with enhanced potency and responses to…

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Guided nuclear exploration increases CTCF target search efficiency

Posted on Dec 2nd, 2019 - By Anders S. Hansen

Nature Chemical Biology, Published online: 02 December 2019; doi:10.1038/s41589-019-0422-3Single-particle tracking and mathematical modeling methods reveal the searching mechanism of CTCF for its cognate sites on DNA. An RNA-binding region in CTCF mediates its trapping in small zones and increases its target search…

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Targeting the interaction of AIMP2-DX2 with HSP70 suppresses cancer development

Posted on Dec 2nd, 2019 - By Semi Lim

Nature Chemical Biology, Published online: 02 December 2019; doi:10.1038/s41589-019-0415-2The cellular stability of an oncogenic factor, AIMP2-DX2, is increased via association with HSP70. Interference with this interaction by a small-molecule compound promotes ubiquitin-mediated degradation of AIMP2-DX2 and reduces cancer cell…

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Resilient living materials built by printing bacterial spores

Posted on Dec 2nd, 2019 - By Lina M. González

Nature Chemical Biology, Published online: 02 December 2019; doi:10.1038/s41589-019-0412-53D printing agarose hydrogels embedded with Bacillus subtilis spores produce custom-shaped materials that are resistant to environmental stresses, while the bacteria maintain the ability to germinate on the surface and respond to…

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Engineering a nicotinamide mononucleotide redox cofactor system for biocatalysis

Posted on Nov 25th, 2019 - By William B. Black

Nature Chemical Biology, Published online: 25 November 2019; doi:10.1038/s41589-019-0402-7Redesign of a glucose dehydrogenase to use nicotinamide mononucleotide (NMN+) instead of NAD(P)+ enables the development of a noncanonical cofactor system that can be used to support redox chemistries both in vitro and in Escherichia…

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Global targeting of functional tyrosines using sulfur-triazole exchange chemistry

Posted on Nov 25th, 2019 - By Heung Sik Hahm

Nature Chemical Biology, Published online: 25 November 2019; doi:10.1038/s41589-019-0404-5Sulfur-triazole exchange (SuTEx) chemistry is a tunable platform for covalent chemoproteomic probes that selectively target tyrosines, used to identify residues with enhanced nucleophilicity and monitor activation of phosphotyrosine…

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Discovery of an antivirulence compound that reverses <i>β</i>-lactam resistance in MRSA

Posted on Nov 25th, 2019 - By Omar M. El-Halfawy

Nature Chemical Biology, Published online: 25 November 2019; doi:10.1038/s41589-019-0401-8A potent inhibitor of the MRSA virulence regulator, GraR, reverses methicillin resistance, inhibits biofilm formation, limits bacterial survival in macrophages and attenuates virulence in vitro, synergizing with cationic antimicrobial…

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A computational framework to explore large-scale biosynthetic diversity

Posted on Nov 25th, 2019 - By Jorge C. Navarro-Muñoz

Nature Chemical Biology, Published online: 25 November 2019; doi:10.1038/s41589-019-0400-9Two bioinformatic tools, BiG-SCAPE and CORASON, enable sequence similarity network and phylogenetic analysis of gene clusters and their families across hundreds of strains and in large datasets, leading to the discovery of new natural…

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Identification of a radical SAM enzyme involved in the synthesis of archaeosine

Posted on Nov 18th, 2019 - By Takashi Yokogawa

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0390-7Euryarchaeal ArcS alone cannot produce G+-containing tRNA but works as a lysine transferase to produce a lysine adduct intermediate, which finally forms G+-containing tRNA in the presence of a newly identified SAM enzyme,…

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The chemical basis of ferroptosis

Posted on Nov 18th, 2019 - By Marcus Conrad

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0408-1This Perspective focuses on the chemical basis of ferroptotic cell death, discussing the prominent role of spontaneous chemical reactions, how they depend on enzyme-catalyzed processes and how to exploit this interplay for therapeutic…

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Site-specific acylation of a bacterial virulence regulator attenuates infection

Posted on Nov 18th, 2019 - By Zhenrun J. Zhang

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0392-5Microbiota-derived butyrate acylation of the key Salmonella enterica transcriptional regulator HilA attenuates virulence of the bacteria, blocking invasion of epithelial cells in vitro and dissemination in…

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Axonal dispatch of iron in neuronal signaling

Posted on Nov 18th, 2019 - By Peng Lei

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0394-3The regulation of brain iron homeostasis, previously thought to be cell autonomous and modulated by local factors in the interstitial fluid, is reported by Wang et al. to be strongly influenced by axonal transport of iron in an activity-dependent and unidirectional manner between functionally associated regions. The supply of iron from the ventral hippocampus to the middle prefrontal cortex subserved an…

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Choosing a mating site

Posted on Nov 18th, 2019 - By Mirella Bucci

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0418-zChoosing a mating…

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Iodine goes viral

Posted on Nov 18th, 2019 - By Caitlin Deane

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0416-1Iodine goes…

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Solo act revealed to be duet

Posted on Nov 18th, 2019 - By Mohamed Atta

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0406-3The last step of archaeosine biosynthesis was found to involve two enzymes, the previously known ArcS with lysine transfer activity and a novel identified radical SAM enzyme named…

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Cutting actin with light

Posted on Nov 18th, 2019 - By Qian Chen

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0410-7Actin cytoskeletal structures are essential for many cellular processes, and cofilin is a key protein for the assembly of these highly dynamic structures. A new cofilin construct enables precise optogenetic control of actin assembly in live…

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Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15

Posted on Nov 4th, 2019 - By Tyler B. Faust

Nature Chemical Biology, Published online: 04 November 2019; doi:10.1038/s41589-019-0378-3Cryo-EM and crystal structural analysis of DDB1–DCAF15–DDA1 in complex with E7820 and RBM39 reveal that aryl-sulfonamides reshape the surface of the cullin RING ligase substrate receptor DCAF15 to bind and degrade the splicing factor…

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Two-site recognition of <i>Staphylococcus aureus</i> peptidoglycan by lysostaphin SH3b

Posted on Nov 4th, 2019 - By Luz S. Gonzalez-Delgado

Nature Chemical Biology, Published online: 04 November 2019; doi:10.1038/s41589-019-0393-4A structural look at the interaction between the SH3b domain of the peptidoglycan endopeptidase lysostaphin and the target for its antistaphylococcal activity, peptidoglycan, reveals a mechanism of bacterial cell wall…

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De novo-designed translation-repressing riboregulators for multi-input cellular logic

Posted on Nov 4th, 2019 - By Jongmin Kim

Nature Chemical Biology, Published online: 04 November 2019; doi:10.1038/s41589-019-0388-1Two programmable riboregulator systems, based on toehold and three-way junction RNA motifs, were designed and validated as robust translational repressors in cells and applied for the construction of logic…

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Structure of an allosteric modulator bound to the CB1 cannabinoid receptor

Posted on Oct 28th, 2019 - By Zhenhua Shao

Nature Chemical Biology, Published online: 28 October 2019; doi:10.1038/s41589-019-0387-2A crystal structure of the GPCR target of endocannabinoid signaling lipids and drugs, CB1, bound to a negative allosteric modulator (NAM) and an agonist, shows that the NAM binds to a membrane-embedded site reminiscent of the binding site of…

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Uncoupling of PARP1 trapping and inhibition using selective PARP1 degradation

Posted on Oct 28th, 2019 - By Shuai Wang

Nature Chemical Biology, Published online: 28 October 2019; doi:10.1038/s41589-019-0379-2Small molecules that achieve selective PARP1 degradation were developed that block both the catalytic activity and scaffolding effects of PARP1, enabling the decoupling of PARP1 inhibition and PARP1…

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Author Correction: MCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOG

Posted on Oct 23rd, 2019 - By Louise Fets

Nature Chemical Biology, Published online: 23 October 2019; doi:10.1038/s41589-019-0409-0Author Correction: MCT2 mediates concentration-dependent inhibition of glutamine metabolism by…

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Extracellular phosphorylation in axon pathfinding

Posted on Oct 21st, 2019 - By Patricia T. Yam

Nature Chemical Biology, Published online: 21 October 2019; doi:10.1038/s41589-019-0383-6The growth and guidance of axons dictate their trajectories and are critical for neural-circuit formation. Research in this issue uncovers a new mechanism for regulation of axon growth and guidance that acts via extracellular phosphorylation of a…

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An inside job

Posted on Oct 21st, 2019 - By Caitlin Deane

Nature Chemical Biology, Published online: 21 October 2019; doi:10.1038/s41589-019-0395-2An inside…

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Molecular basis for the P450-catalyzed C–N bond formation in indolactam biosynthesis

Posted on Oct 21st, 2019 - By Fei He

Nature Chemical Biology, Published online: 21 October 2019; doi:10.1038/s41589-019-0380-9Structural and functional analyses of two cytochrome P450 monooxygenases reveal how they catalyze C–N bond formation via a diradical mechanism and are able to accommodate a variety of substrates to form either indolactam or tricyclic…

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Disorder guides order

Posted on Oct 21st, 2019 - By Yiyun Song

Nature Chemical Biology, Published online: 21 October 2019; doi:10.1038/s41589-019-0398-zDisorder guides…

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Higher-order epistasis shapes the fitness landscape of a xenobiotic-degrading enzyme

Posted on Oct 21st, 2019 - By Gloria Yang

Nature Chemical Biology, Published online: 21 October 2019; doi:10.1038/s41589-019-0386-3Ancestral protein reconstruction followed by biochemical and structural analyses characterizes the evolutionary trajectory of methyl-parathion hydrolase from an ancestral dihydrocoumarin hydrolase through the accumulation of five key…

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Long-range tedatmporal coordination of gene expression in synthetic microbial consortia

Posted on Oct 14th, 2019 - By Jae Kyoung Kim

Nature Chemical Biology, Published online: 14 October 2019; doi:10.1038/s41589-019-0372-9Synthetic microbial consortia were applied to demonstrate that oscillatory gene expression in a bacterial population can be propagated over longer distances by activating a localized positive feedback…

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Structural basis of sequence-specific Holliday junction cleavage by MOC1

Posted on Oct 14th, 2019 - By Huajian Lin

Nature Chemical Biology, Published online: 14 October 2019; doi:10.1038/s41589-019-0377-4Crystal structural and biochemical analysis of the chloroplast-localized Holliday junction (HJ) resolvase MOC1 in Zea mays reveals that ZmMOC1 uses a unique β-hairpin structure and a two-metal ion catalysis mechanism to recognize and cleave…

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p63 is a cereblon substrate involved in thalidomide teratogenicity

Posted on Oct 7th, 2019 - By Tomoko Asatsuma-Okumura

Nature Chemical Biology, Published online: 07 October 2019; doi:10.1038/s41589-019-0366-7Zebrafish p63 isoforms were identified as thalidomide-dependent neosubstrates of the cereblon-containing E3 ligase complex. ∆Np63α and TAp63α are responsible for thalidomide-induced malformations of pectoral fins and otic vesicles,…

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Mapping spatial transcriptome with light-activated proximity-dependent RNA labeling

Posted on Oct 7th, 2019 - By Pengchong Wang

Nature Chemical Biology, Published online: 07 October 2019; doi:10.1038/s41589-019-0368-5A light-activated RNA labeling method was developed to determine spatial organization of a transcriptome and found that ribosomal proteins and oxidative phosphorylation pathway proteins are highly enriched at the outer mitochondrial…

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Axonal iron transport in the brain modulates anxiety-related behaviors

Posted on Oct 7th, 2019 - By Zhuo Wang

Nature Chemical Biology, Published online: 07 October 2019; doi:10.1038/s41589-019-0371-xIron is transported from the ventral hippocampus to the medial prefrontal cortex unidirectionally in the brain via axonal projections. This transport is involved in mediating anxiety and the anxiolytic effects of…

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A small molecule interacts with VDAC2 to block mouse BAK-driven apoptosis

Posted on Oct 7th, 2019 - By Mark F. van Delft

Nature Chemical Biology, Published online: 07 October 2019; doi:10.1038/s41589-019-0365-8A phenotypic screen led to the identification of potent inhibitors of mouse BAK-driven apoptosis. The compounds interact with VDAC2 and stabilize its interaction with BAK, blocking apoptosis at an early stage to preserve long-term cell…

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A lipid site shapes the agonist response of a pentameric ligand-gated ion channel

Posted on Oct 7th, 2019 - By Camille M. Hénault

Nature Chemical Biology, Published online: 07 October 2019; doi:10.1038/s41589-019-0369-4A crystal structure of prokaryotic pentameric ligand-gated ion channel ELIC reveals a lipid-binding site at the interface between subunits that is shaped by a flexible helix important for channel desensitization upon lipid…

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A family of radical halogenases for the engineering of amino-acid-based products

Posted on Sep 23rd, 2019 - By Monica E. Neugebauer

Nature Chemical Biology, Published online: 23 September 2019; doi:10.1038/s41589-019-0355-xStructural characterization of the amino-acid-modifying radical halogenase BesD and identification of new members of this protein family provides insight into the enzymatic mechanism and enables biocatalytic production of halogenated amino…

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The morphogen Sonic hedgehog inhibits its receptor Patched by a pincer grasp mechanism

Posted on Sep 23rd, 2019 - By Amalie F. Rudolf

Nature Chemical Biology, Published online: 23 September 2019; doi:10.1038/s41589-019-0370-yCholesterol can function as both a substrate and an inhibitor of the Hedgehog receptor Patched. Structural analysis and molecular dynamics simulations reveal that cholesterol inhibits Patched by inserting into its extracellular…

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Near-equilibrium glycolysis supports metabolic homeostasis and energy yield

Posted on Sep 23rd, 2019 - By Junyoung O. Park

Nature Chemical Biology, Published online: 23 September 2019; doi:10.1038/s41589-019-0364-9A 2H and 13C tracing strategy was used for efficient determination of glycolytic thermodynamics, revealing near-equilibrium glycolytic steps enabling rapid flux adaptation and, in Clostridium cellulolyticum, enhanced ATP…

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Colibactin comes to light

Posted on Sep 20th, 2019 - By Caitlin Deane

Nature Chemical Biology, Published online: 20 September 2019; doi:10.1038/s41589-019-0373-8Colibactin comes to…

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First contact

Posted on Sep 20th, 2019 - By Yiyun Song

Nature Chemical Biology, Published online: 20 September 2019; doi:10.1038/s41589-019-0375-6First…

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A NAMe-tag for ALS

Posted on Sep 20th, 2019 - By Mirella Bucci

Nature Chemical Biology, Published online: 20 September 2019; doi:10.1038/s41589-019-0374-7A NAMe-tag for…

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The root of the cause

Posted on Sep 20th, 2019 - By Grant Miura

Nature Chemical Biology, Published online: 20 September 2019; doi:10.1038/s41589-019-0376-5The root of the…

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DNA repair complex licenses acetylation of H2A.Z.1 by KAT2A during transcription

Posted on Sep 16th, 2019 - By M. Semer

Nature Chemical Biology, Published online: 16 September 2019; doi:10.1038/s41589-019-0354-yKAT2A acetylates histone variant H2A.Z to regulate transactivation of XPC and RAR positively regulated genes. The DNA repair complex XPC–RAD23–CEN2 interacts with H2A.Z and KAT2A to license the latter’s histone acetyltransferase…

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Versatile biomanufacturing through stimulus-responsive cell–material feedback

Posted on Sep 16th, 2019 - By Zhuojun Dai

Nature Chemical Biology, Published online: 16 September 2019; doi:10.1038/s41589-019-0357-8Encapsulation of engineered bacteria in environmentally responsive materials enables on-demand protein production coupled to downstream processes such as protein purification, on-chip enzyme kinetics and metabolic production of fatty…

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Development of targeted protein degradation therapeutics

Posted on Sep 16th, 2019 - By Philip P. Chamberlain

Nature Chemical Biology, Published online: 16 September 2019; doi:10.1038/s41589-019-0362-yThis Perspective summarizes recent discoveries that have laid the foundation for targeted degradation therapeutics and discusses the current state of understanding and consideration involved in developing these protein…

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Dynamic membrane topology in an unassembled membrane protein

Posted on Sep 9th, 2019 - By Maximilian Seurig

Nature Chemical Biology, Published online: 09 September 2019; doi:10.1038/s41589-019-0356-9The topology of homodimeric membrane protein EmrE is dynamic and includes unassisted flipping of an N-terminal helix in and out of the membrane long after co-translational insertion. Dimerization locks the helix to limit topological…

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Cargo adaptors regulate stepping and force generation of mammalian dynein–dynactin

Posted on Sep 9th, 2019 - By Mohamed M. Elshenawy

Nature Chemical Biology, Published online: 09 September 2019; doi:10.1038/s41589-019-0352-0Single-molecule analysis revealed that the velocity and force generation of the mammalian dynein–dynactin complex is regulated by activating adaptors and tail–tail interactions between two…

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The tail wags the motor

Posted on Sep 9th, 2019 - By Richard J. McKenney

Nature Chemical Biology, Published online: 09 September 2019; doi:10.1038/s41589-019-0367-6Cytoplasmic dynein is a complex molecular motor that steps along microtubules. Advanced biophysical measurements reveal a surprising role for the dynein tail domain in the allosteric control of dynein’s mechanochemistry within assemblies composed of multiple dynein…

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mRNA structure determines modification by pseudouridine synthase 1

Posted on Sep 2nd, 2019 - By Thomas M. Carlile

Nature Chemical Biology, Published online: 02 September 2019; doi:10.1038/s41589-019-0353-zAn in vitro method was developed to screen mRNA sites for psedouridine modification by specific pseudouridylating enzymes and identify an RNA structural motif for Pus1, which can be used to predict new pseudouridylated mRNA targets in…

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A blue light receptor that mediates RNA binding and translational regulation

Posted on Aug 26th, 2019 - By Anna M. Weber

Nature Chemical Biology, Published online: 26 August 2019; doi:10.1038/s41589-019-0346-yA light-oxygen-voltage photoreceptor was found to bind short RNA stem loops in a light-dependent manner, which can be harnessed to regulate gene expression in bacteria and mammalian…

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Fosmidomycin biosynthesis diverges from related phosphonate natural products

Posted on Aug 26th, 2019 - By Elizabeth I. Parkinson

Nature Chemical Biology, Published online: 26 August 2019; doi:10.1038/s41589-019-0343-1The biosynthetic pathway for the phosphonate natural product dehydrofosmidomycin differs from that of the related compound FR-900098, involving rearrangement of a two-carbon phosphonate precursor catalyzed by a 2-oxoglutarate-dependent…

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Extracellular phosphorylation drives the formation of neuronal circuitry

Posted on Aug 26th, 2019 - By Hidekiyo Harada

Nature Chemical Biology, Published online: 26 August 2019; doi:10.1038/s41589-019-0345-zVia its receptor LRP5, Wnt3a stimulates axonal growth in retinal ganglion neurons. Phosphorylation of co-receptor RGMb by VLK induces LRP5 internalization to limit Wnt3a signaling and reduce axon…

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CRISPR-Cas9 screens identify regulators of antibody–drug conjugate toxicity

Posted on Aug 26th, 2019 - By C. Kimberly Tsui

Nature Chemical Biology, Published online: 26 August 2019; doi:10.1038/s41589-019-0342-2A series of genome-wide and targeted CRISPR screens uncovered regulators of antibody–drug conjugate (ADC) toxicity. Depletion of sialic acids was found to enhance ADC lysosomal delivery, in part by reducing ADC…

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Breaking up is hard to do

Posted on Aug 26th, 2019 - By Heather A. Van Epps

Nature Chemical Biology, Published online: 26 August 2019; doi:10.1038/s41589-019-0351-1A comprehensive genetic screen reveals new cellular trafficking factors and linker-dependent requirements for antibody–drug conjugate (ADC) cytotoxicity. These new insights may guide the design of optimized…

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Publisher Correction: Pharmacological targeting of the unfolded protein response for disease intervention

Posted on Aug 22nd, 2019 - By Claudio Hetz

Nature Chemical Biology, Published online: 22 August 2019; doi:10.1038/s41589-019-0363-xPublisher Correction: Pharmacological targeting of the unfolded protein response for disease…

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Toll-like receptor mediated inflammation requires FASN-dependent MYD88 palmitoylation

Posted on Aug 19th, 2019 - By Young-Chan Kim

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0344-0Inhibition of fatty acid synthase, FASN, blocks innate immune signaling through TLR/MyD88 in neutrophils by blocking palmitoylation of MyD88 by palmitoyltransferase zDHHC6 and improves outcomes in two mouse models of…

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Breathing the same air

Posted on Aug 19th, 2019 - By Grant Miura

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0359-6Breathing the same…

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Lights, enzyme, action!

Posted on Aug 19th, 2019 - By Caitlin Deane

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0360-0Lights, enzyme,…

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