Publisher Correction: Structural insights into β-1,3-glucan cleavage by a glycoside hydrolase family

Posted on Jun 25th, 2020 - By Camila R. Santos

Nature Chemical Biology, Published online: 25 June 2020; doi:10.1038/s41589-020-0590-1Publisher Correction: Structural insights into β-1,3-glucan cleavage by a glycoside hydrolase…

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The uninhibited pathway is not worth studying

Posted on Jun 22nd, 2020 - By Michael E. Pacold

Nature Chemical Biology, Published online: 22 June 2020; doi:10.1038/s41589-020-0562-5Glucose 6-phosphate dehydrogenase (G6PD) stands at the head of the pentose phosphate pathway, which is responsible for nucleotide synthesis. The identification and thorough validation of an improved G6PD inhibitor provide a valuable new tool compound for studying…

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Groovy RNA polymerase

Posted on Jun 22nd, 2020 - By Mirella Bucci

Nature Chemical Biology, Published online: 22 June 2020; doi:10.1038/s41589-020-0582-1Groovy RNA…

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Dissecting the Pol II transcription cycle and derailing cancer with CDK inhibitors

Posted on Jun 22nd, 2020 - By Pabitra K. Parua

Nature Chemical Biology, Published online: 22 June 2020; doi:10.1038/s41589-020-0563-4This Review provides insights into transcriptional regulation, and vulnerabilities of cancer cells to disruption of cyclin-dependent kinase (CDK)-mediated regulation of Pol II transcription, revealed with small-molecule CDK…

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Structural insight into the formation of lipoprotein-β-barrel complexes

Posted on Jun 22nd, 2020 - By Raquel Rodríguez-Alonso

Nature Chemical Biology, Published online: 22 June 2020; doi:10.1038/s41589-020-0575-0A structural and biochemical study of bacterial β-barrel assembly machinery component BamA with transport substrate RcsF shows an inward-open conformation with RcsF trapped inside the β-barrel lumen and suggests a push–pull substrate export…

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Spectroscopic coherent Raman imaging of <i>Caenorhabditis elegans</i> reveals lipid particle diversity

Posted on Jun 22nd, 2020 - By Wei-Wen Chen

Nature Chemical Biology, Published online: 22 June 2020; doi:10.1038/s41589-020-0565-2A Raman-based imaging approach that can distinguish closely related chemical species used to characterize the distribution of lipids throughout the body of intact Caenorhabditis elegans worms shows that the epidermis is an important fat-storage…

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Discovering Nature’s super glue

Posted on Jun 22nd, 2020 - By Zhi Zeng

Nature Chemical Biology, Published online: 22 June 2020; doi:10.1038/s41589-020-0586-xMolecular glues induce novel protein–protein interactions to modulate protein function and downstream biology. A recent study unveils manumycin polyketides with multiple electrophilic centers as covalent molecular glues between UBR7 and…

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Taking out the trash

Posted on Jun 22nd, 2020 - By Grant Miura

Nature Chemical Biology, Published online: 22 June 2020; doi:10.1038/s41589-020-0581-2Taking out the…

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Enzymes knuckle down to the job

Posted on Jun 17th, 2020 - By Paul H. Walton

Nature Chemical Biology, Published online: 17 June 2020; doi:10.1038/s41589-020-0585-yA suite of new enzymes reveals more on how Nature breaks down plant-based polysaccharides and how these enzymes might be harnessed in the utilization of plant-based…

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Unraveling proteasome engagement

Posted on Jun 15th, 2020 - By Cameron G. Roberts

Nature Chemical Biology, Published online: 15 June 2020; doi:10.1038/s41589-020-0573-2A new study reveals that, in addition to its longstanding role in recruiting proteins to the proteasome, ubiquitination can also induce a structural destabilization that allows the target protein to be efficiently unraveled for…

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Single-molecule analysis reveals agonist-specific dimer formation of µ-opioid receptors

Posted on Jun 15th, 2020 - By Jan Möller

Nature Chemical Biology, Published online: 15 June 2020; doi:10.1038/s41589-020-0566-1Single-molecule and super-resolution approaches define a monomer–dimer equilibrium of µ-opioid receptors and show that receptors form agonist-induced dimers coincident with β-arrestin2 binding to…

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In vitro prototyping and rapid optimization of biosynthetic enzymes for cell design

Posted on Jun 15th, 2020 - By Ashty S. Karim

Nature Chemical Biology, Published online: 15 June 2020; doi:10.1038/s41589-020-0559-0The iPROBE platform accelerates the design and optimization of engineered biosynthetic pathways using a combination of cell-free protein synthesis, in vitro pathway assembly and a scoring system to identify high-performing…

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

Posted on Jun 12th, 2020 - By Gloria Yang

Nature Chemical Biology, Published online: 12 June 2020; doi:10.1038/s41589-020-0588-8Author Correction: Higher-order epistasis shapes the fitness landscape of a xenobiotic-degrading…

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Use of paramagnetic <sup>19</sup>F NMR to monitor domain movement in a glutamate transporter homolog

Posted on Jun 8th, 2020 - By Yun Huang

Nature Chemical Biology, Published online: 08 June 2020; doi:10.1038/s41589-020-0561-6A 19F-NMR-based method monitoring the conformational dynamics of the glutamate transporter GltPh identified one inward- and two outward-facing states, including one unanticipated outward-facing state that was characterized by…

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Comparative tRNA sequencing and RNA mass spectrometry for surveying tRNA modifications

Posted on Jun 8th, 2020 - By Satoshi Kimura

Nature Chemical Biology, Published online: 08 June 2020; doi:10.1038/s41589-020-0558-1A combination of tRNA sequencing and mass spectrometry was developed to profile tRNA modification enabling identification of a new modification acacp3U and the presence of cytosine-to-pseudouracil RNA editing in Vibrio…

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Discovery of small-molecule enzyme activators by activity-based protein profiling

Posted on Jun 8th, 2020 - By Bernard P. Kok

Nature Chemical Biology, Published online: 08 June 2020; doi:10.1038/s41589-020-0555-4Activity-based protein profiling (ABPP) was used to identify and optimize bioactive, selective pharmacological enzyme activators of the serine hydrolase LYPLAL1, which improved the metabolic defects of diet-induced obese…

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Rolf Huisgen (1920–2020)

Posted on Jun 2nd, 2020 - By Dirk Trauner

Nature Chemical Biology, Published online: 02 June 2020; doi:10.1038/s41589-020-0571-4Rolf Huisgen left us on 26 March 2020, just three months shy of his 100th birthday. His work has had an enormous influence on chemical biology, ranging from new methods for the synthesis of chemical probes to “click chemistry” and its application to in vivo…

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Publisher Correction: Complete reconstitution of the diverse pathways of gentamicin B biosynthesis

Posted on Jun 2nd, 2020 - By Yeon Hee Ban

Nature Chemical Biology, Published online: 02 June 2020; doi:10.1038/s41589-020-0577-yPublisher Correction: Complete reconstitution of the diverse pathways of gentamicin B…

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Selective <i>N</i>-glycan editing on living cell surfaces to probe glycoconjugate function

Posted on Jun 1st, 2020 - By Feng Tang

Nature Chemical Biology, Published online: 01 June 2020; doi:10.1038/s41589-020-0551-8Cellular glycosylation facilitates molecular recognition of cells and biomolecules. A two-step N-glycan editing method enables selective glycoform ‘deletion’ and ‘insertion’ of new glycans, which can be used to probe their biological…

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Site-specific ubiquitination affects protein energetics and proteasomal degradation

Posted on Jun 1st, 2020 - By Emma C. Carroll

Nature Chemical Biology, Published online: 01 June 2020; doi:10.1038/s41589-020-0556-3Using a new method to generate site-specific monoubiquitinated proteins, the authors find monoubiquitination has a site-specific effect on protein stability and proteasomal…

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An allosteric modulator binds to a conformational hub in the β<sub>2</sub> adrenergic receptor

Posted on Jun 1st, 2020 - By Xiangyu Liu

Nature Chemical Biology, Published online: 01 June 2020; doi:10.1038/s41589-020-0549-2A negative allosteric modulator of the G-protein-coupled receptor β2-adrenergic receptor binds to a membrane-facing surface adjacent to a molecular switch for receptor activation, and its binding disrupts a water-mediated polar network stabilizing an inactive switch…

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Identification of a potent and selective covalent Pin1 inhibitor

Posted on Jun 1st, 2020 - By Benika J. Pinch

Nature Chemical Biology, Published online: 01 June 2020; doi:10.1038/s41589-020-0550-9A highly selective covalent peptide inhibitor of the peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is used to show that Pin1 cooperates with mutant KRAS to promote pancreatic ductal adenocarcinoma (PDAC)…

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Pyridoxal-5′-phosphate-dependent alkyl transfer in nucleoside antibiotic biosynthesis

Posted on Jun 1st, 2020 - By Zheng Cui

Nature Chemical Biology, Published online: 01 June 2020; doi:10.1038/s41589-020-0548-3Rather than a typical S-adenosylmethionine-dependent alkyltransferase, the installation of the N-alkylamine linker in several nucleoside antibiotics is catalyzed via γ-replacement by a pyridoxal-5′-phosphate-dependent…

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Structural insights into β-1,3-glucan cleavage by a glycoside hydrolase family

Posted on May 25th, 2020 - By Camila R. Santos

Nature Chemical Biology, Published online: 25 May 2020; doi:10.1038/s41589-020-0554-5Comprehensive informatic, structural and biochemical characterization of the GH128 family defines subgroups of glycoside hydrolase enzymes with unique recognition and cleavage mechanisms for 1,3-beta-glucan polysaccharide…

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m<sup>6</sup>A-binding YTHDF proteins promote stress granule formation

Posted on May 25th, 2020 - By Ye Fu

Nature Chemical Biology, Published online: 25 May 2020; doi:10.1038/s41589-020-0524-yImaging studies revealed that m6A-binding YTHDF proteins promoted phase separation of core proteins of stress granules by reducing the critical size and activation energy barrier, thus promoting the formation of stress granules in…

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PGE1 and PGA1 bind to Nurr1 and activate its transcriptional function

Posted on May 25th, 2020 - By Sreekanth Rajan

Nature Chemical Biology, Published online: 25 May 2020; doi:10.1038/s41589-020-0553-6Prostaglandins PGE1 and PGA1 have neuroprotective effects by enhancing the transcriptional activity of Nurr1 by directly binding to its ligand-binding domain and upregulating their target genes implicated in Parkinson’s…

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Yes (again) to local NO

Posted on May 22nd, 2020 - By Emrah Eroglu

Nature Chemical Biology, Published online: 22 May 2020; doi:10.1038/s41589-020-0552-7A pair of fluorescent indicator-tagged DNA-duplex scaffolds permit assessments of nitric oxide (NO) production on cell surfaces and in intracellular networks. The application of these nanoprobes indicates formations of local NO signals that might conserve cancer cell…

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A tail of CRY selectivity

Posted on May 22nd, 2020 - By Julia Lara

Nature Chemical Biology, Published online: 22 May 2020; doi:10.1038/s41589-020-0531-zThe discovery of selective modulators of two Cryptochrome isoforms, CRY1 and CRY2, permits a deeper understanding of how circadian clock proteins impact diverse aspects of our daily 24-h rhythms and how this intersects with metabolic pathways relevant to…

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Chromatin as a key consumer in the metabolite economy

Posted on May 22nd, 2020 - By Katharine L. Diehl

Nature Chemical Biology, Published online: 22 May 2020; doi:10.1038/s41589-020-0517-xThis Perspective highlights emerging themes in the inter-regulation of the genome and metabolism via chromatin, including nonenzymatic histone modifications, cofactor-promiscuous chromatin-modifying enzymes, and subnucleocytoplasmic metabolite…

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15 years of <i>Nature Chemical Biology</i>

Nature Chemical Biology, Published online: 22 May 2020; doi:10.1038/s41589-020-0560-7Over the past decade and a half, chemical biology has crystallized as a discipline and extended its reach into new scientific areas, but the field’s greatest promise lies…

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Greatest hits

Nature Chemical Biology, Published online: 22 May 2020; doi:10.1038/s41589-020-0546-5We present a selection of papers published in Nature Chemical Biology over the past five years that reflect the diversity and excitement of chemical biology…

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Voices of chemical biology

Nature Chemical Biology, Published online: 22 May 2020; doi:10.1038/s41589-020-0543-8We asked a collection of chemical biologists, “What was the most exciting research achievement or technology innovation in chemical biology in the last five years?” and reveal some of the perspectives we…

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The developing toolkit of continuous directed evolution

Posted on May 22nd, 2020 - By Mary S. Morrison

Nature Chemical Biology, Published online: 22 May 2020; doi:10.1038/s41589-020-0532-yThis historical Perspective on continuous directed evolution focuses on laboratory approaches that enable greater understanding of evolving molecular populations and offer investigators tools to guide the emergence of new biomolecular…

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Design of orthogonal regulatory systems for modulating gene expression in plants

Posted on May 18th, 2020 - By Michael S. Belcher

Nature Chemical Biology, Published online: 18 May 2020; doi:10.1038/s41589-020-0547-4Engineering of yeast transcription factors and design of hybrid DNA promoter elements have resulted in a toolkit for tunable and orthogonal regulation of gene expression in Arabidopsis thaliana and Nicotiana benthamiana…

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Author Correction: Plasma membranes are asymmetric in lipid unsaturation, packing and protein shape

Posted on May 15th, 2020 - By J. H. Lorent

Nature Chemical Biology, Published online: 15 May 2020; doi:10.1038/s41589-020-0564-3Author Correction: Plasma membranes are asymmetric in lipid unsaturation, packing and protein…

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A nucleotide-switch mechanism mediates opposing catalytic activities of Rel enzymes

Posted on May 11th, 2020 - By Hedvig Tamman

Nature Chemical Biology, Published online: 11 May 2020; doi:10.1038/s41589-020-0520-2Structural and smFRET analysis reveals the mechanism of opposing catalytic activities of bifunctional Rel enzymes; that is, activation of one of the catalytic domains leads to allosteric inactivation of the…

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Discovery of a NAPE-PLD inhibitor that modulates emotional behavior in mice

Posted on May 11th, 2020 - By Elliot D. Mock

Nature Chemical Biology, Published online: 11 May 2020; doi:10.1038/s41589-020-0528-7An inhibitor of NAPE-PLD involved in lipid biosynthesis lowers levels of the endocannabinoid anandamide and other N-acylethanolamines in cells and mouse brain and activates the hypothalamus–pituitary–adrenal axis and impaired fear…

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Structural and mechanistic insights into 5-lipoxygenase inhibition by natural products

Posted on May 11th, 2020 - By Nathaniel C. Gilbert

Nature Chemical Biology, Published online: 11 May 2020; doi:10.1038/s41589-020-0544-7Structures of 5-lipoxygenase (5-LOX) reveal that NDGA disturbs regions that shield the active site while AKBA binds an allosteric site. NDGA inhibits 5-LOX activity using its redox-active function, while AKBA changes the enzyme’s…

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A small molecule G6PD inhibitor reveals immune dependence on pentose phosphate pathway

Posted on May 11th, 2020 - By Jonathan M. Ghergurovich

Nature Chemical Biology, Published online: 11 May 2020; doi:10.1038/s41589-020-0533-xIdentification of an improved glucose-6-phosphate dehydrogenase (G6PD) inhibitor G6PDi-1 blocks G6PD activity more robustly than the widely cited antagonist DHEA. G6PDi-1 treatment blocks T cell cytokine production and neutrophil oxidative…

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Structural basis for selectivity in a highly reducing type II polyketide synthase

Posted on May 4th, 2020 - By Danyao Du

Nature Chemical Biology, Published online: 04 May 2020; doi:10.1038/s41589-020-0530-0Structures of the ketosynthase–chain length factor complex from ishigamide biosynthesis, cross-linked to the acyl carrier protein, reveal the molecular interactions between these domains and how the reaction pocket limits rounds of product…

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Plasma membranes are asymmetric in lipid unsaturation, packing and protein shape

Posted on May 4th, 2020 - By J. H. Lorent

Nature Chemical Biology, Published online: 04 May 2020; doi:10.1038/s41589-020-0529-6Lipidomics across the bilayer membrane plus biophysical and fluorescence approaches find asymmetry in phospholipid unsaturation and localization of protein transmembrane domains based on their ability to pack within the different membrane…

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Asymmetry across the membrane

Posted on May 4th, 2020 - By Maria Makarova

Nature Chemical Biology, Published online: 04 May 2020; doi:10.1038/s41589-020-0545-6A combination of biochemical and biophysical techniques to document the asymmetric distribution of lipids, with a particular focus on the acyl tails, in mammalian cell membranes show that protein transmembrane domains are similarly…

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TRUPATH, an open-source biosensor platform for interrogating the GPCR transducerome

Posted on May 4th, 2020 - By Reid H. J. Olsen

Nature Chemical Biology, Published online: 04 May 2020; doi:10.1038/s41589-020-0535-8Development of BRET sensors for nearly all major G proteins show that GPCR–G-protein coupling ranges from promiscuous to extremely specific, Switch III is a novel site for G-protein engineering, and optimal donor–acceptor positioning is…

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A metabolic labeling method detects m<sup>6</sup>A transcriptome-wide at single base resolution

Posted on Apr 27th, 2020 - By Xiao Shu

Nature Chemical Biology, Published online: 27 April 2020; doi:10.1038/s41589-020-0526-9The authors developed a metabolic labeling method via incorporation of allyl-SAM analogs to profile transcriptome-wide m6A at base resolution, which enables identification of m6A motifs and clustered m6A…

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Antibody-free enzyme-assisted chemical approach for detection of <i>N</i><sup>6</sup>-methyladenosine

Posted on Apr 27th, 2020 - By Ye Wang

Nature Chemical Biology, Published online: 27 April 2020; doi:10.1038/s41589-020-0525-xAn antibody-independent m6A profiling method called m6A-SEAL was developed via turning m6A into stable dm6A after treatment by FTO and DTT. This method exhibits better reliability in detection of transcriptome-wide m6A sites in humans and…

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Viewing spikes

Posted on Apr 22nd, 2020 - By Mirella Bucci

Nature Chemical Biology, Published online: 22 April 2020; doi:10.1038/s41589-020-0538-5Viewing…

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Know your neighbors

Posted on Apr 22nd, 2020 - By Grant Miura

Nature Chemical Biology, Published online: 22 April 2020; doi:10.1038/s41589-020-0537-6Know your…

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Anti-HIV agents inspired by antibodies

Posted on Apr 22nd, 2020 - By Shan Su

Nature Chemical Biology, Published online: 22 April 2020; doi:10.1038/s41589-020-0521-1Emergence of drug resistance limits the efficacy of HIV drugs, which currently requires life-long administration. In vitro high-throughput screening for competition with a broadly neutralizing antibody of HIV identified a small molecule that extends the strategies for targeting…

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A reaction chamber

Posted on Apr 22nd, 2020 - By Yiyun Song

Nature Chemical Biology, Published online: 22 April 2020; doi:10.1038/s41589-020-0539-4A reaction…

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Flavin doesn’t put all oxygens in one basket

Posted on Apr 22nd, 2020 - By David Leys

Nature Chemical Biology, Published online: 22 April 2020; doi:10.1038/s41589-020-0523-zOxygen activation mechanisms catalyzed by flavin cofactors are established for electron transfer (oxidases) and C4a covalent flavin–oxygen adduct formation (oxygen-inserting monooxygenases). A new paradigm for oxygen insertion involving a flavin-N5-aminoperoxide intermediate has now been discovered in select flavin-dependent…

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An iron–sulfur grip

Posted on Apr 22nd, 2020 - By Caitlin Deane

Nature Chemical Biology, Published online: 22 April 2020; doi:10.1038/s41589-020-0536-7An iron–sulfur…

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How m<sup>6</sup>A sneaks into DNA

Posted on Apr 16th, 2020 - By Paolo Spingardi

Nature Chemical Biology, Published online: 16 April 2020; doi:10.1038/s41589-020-0534-9The biological function and origin of m6A in DNA have been widely debated. A new study demonstrates that the majority of m6A in DNA originates from RNA catabolism via a nucleotide salvage…

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Short disordered protein segment regulates cross-species transmission of a yeast prion

Posted on Apr 13th, 2020 - By Toshinobu Shida

Nature Chemical Biology, Published online: 13 April 2020; doi:10.1038/s41589-020-0516-yThe side chain interaction within the short disordered segment of yeast prion protein Sup35 could affect the conformation of the main chain, alter the transmission barrier between species and regulate its cross-seeding…

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Author Correction: Hitchhiking into the cell

Posted on Apr 8th, 2020 - By Douglas B. Kell

Nature Chemical Biology, Published online: 08 April 2020; doi:10.1038/s41589-020-0540-yAuthor Correction: Hitchhiking into the…

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New codons for efficient production of unnatural proteins in a semisynthetic organism

Posted on Apr 6th, 2020 - By Emil C. Fischer

Nature Chemical Biology, Published online: 06 April 2020; doi:10.1038/s41589-020-0507-zSystematic characterization of codons using the unnatural base pair dNaM·dTPT3 leads to the discovery of nine new functional codon–anticodon pairs, three of which are shown to be orthogonally decoded by ribosomes and allow incorporation of up to three noncanonical amino acids in Escherichia…

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Topology-dependent interference of synthetic gene circuit function by growth feedback

Posted on Apr 6th, 2020 - By Rong Zhang

Nature Chemical Biology, Published online: 06 April 2020; doi:10.1038/s41589-020-0509-xSynthetic circuit-host interactions affect the performance synthetic biology systems. Analysis of two bi-stable switch circuits reveals differential effects of host growth on circuit memory, which is dependent on the network topology of the…

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Discovery of a selective inhibitor of doublecortin like kinase 1

Posted on Apr 6th, 2020 - By Fleur M. Ferguson

Nature Chemical Biology, Published online: 06 April 2020; doi:10.1038/s41589-020-0506-0A highly selective inhibitor of the DCLK1/2 kinases is used to uncover the consequences of DCLK1 inhibition on viability, phosphosignaling and the transcriptome in patient-derived organoid models of pancreatic ductal…

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Drug antagonism and single-agent dominance result from differences in death kinetics

Posted on Apr 6th, 2020 - By Ryan Richards

Nature Chemical Biology, Published online: 06 April 2020; doi:10.1038/s41589-020-0510-4Drug combinations consisting of two cell death-targeting drugs are enriched for antagonism and ‘single-agent dominance’, where the faster-acting drug suppresses the slower-acting drug due to inhibitory crosstalk between cell death…

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Ribosomes read new languages

Posted on Apr 6th, 2020 - By Michael C. Jewett

Nature Chemical Biology, Published online: 06 April 2020; doi:10.1038/s41589-020-0522-0Using new letters of DNA to encode information promises to expand the genetic code in a transformative way. A new semisynthetic organism has been created that uses 67 codons for protein biosynthesis, with three new codons based on unnatural…

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Author Correction: Illustrating human PLD

Posted on Mar 31st, 2020 - By Lei Zheng

Nature Chemical Biology, Published online: 31 March 2020; doi:10.1038/s41589-020-0527-8Author Correction: Illustrating human…

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A masked zinger to block GPX4

Posted on Mar 30th, 2020 - By Stefan G. Kathman

Nature Chemical Biology, Published online: 30 March 2020; doi:10.1038/s41589-020-0511-3Ferroptosis induced by GPX4 inhibition offers promise for killing drug-resistant cancer cells, yet current GPX4 inhibitors lack selectivity. The discovery of masked nitrile oxide electrophiles as selective prodrug inhibitors of GPX4 points to an attractive path for chemically inducing…

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Selective covalent targeting of GPX4 using masked nitrile-oxide electrophiles

Posted on Mar 30th, 2020 - By John K. Eaton

Nature Chemical Biology, Published online: 30 March 2020; doi:10.1038/s41589-020-0501-5Nitrile-oxide electrophiles were identified as covalent inhibitors of GPX4 that exhibit increased selectivity and reduced off-target effects relative to chloroacetamide-based…

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Isoform-selective regulation of mammalian cryptochromes

Posted on Mar 30th, 2020 - By Simon Miller

Nature Chemical Biology, Published online: 30 March 2020; doi:10.1038/s41589-020-0505-1Cell-based phenotypic screening of small-molecule circadian clock modulators identified isoform-selective compounds for highly homologous clock proteins CRY1 and CRY2, revealing a key role of the disordered C-terminal region in compound…

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The origin of genomic <i>N</i><sup>6</sup>-methyl-deoxyadenosine in mammalian cells

Posted on Mar 23rd, 2020 - By Michael U. Musheev

Nature Chemical Biology, Published online: 23 March 2020; doi:10.1038/s41589-020-0504-2A metabolic labeling method reveals that genomic N6-methyl-deoxyadenosine in mammalian cell lines originates not from direct methylation in DNA, but from a misincorporation of the metabolite of…

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An aminoacylation ribozyme evolved from a natural tRNA-sensing T-box riboswitch

Posted on Mar 23rd, 2020 - By Satoshi Ishida

Nature Chemical Biology, Published online: 23 March 2020; doi:10.1038/s41589-020-0500-6The authors develop a ribozyme, Tx2.1, that is capable of aminoacylating tRNA with specificity for the anticodon from directed evolution of a T-box riboswitch. Tx2.1 could be used to charge non-natural amino acids in an in vitro translation…

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A tell-tale absence

Posted on Mar 20th, 2020 - By Caitlin Deane

Nature Chemical Biology, Published online: 20 March 2020; doi:10.1038/s41589-020-0513-1A tell-tale…

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Tick tock

Posted on Mar 20th, 2020 - By Yiyun Song

Nature Chemical Biology, Published online: 20 March 2020; doi:10.1038/s41589-020-0515-zTick…

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Unifying principles of bifunctional, proximity-inducing small molecules

Posted on Mar 20th, 2020 - By Christopher J. Gerry

Nature Chemical Biology, Published online: 20 March 2020; doi:10.1038/s41589-020-0469-1This Perspective describes the chemical and biophysical principles common to all bifunctional, proximity-inducing small molecules. It also discusses the underappreciated diversity of their chemical structures and biological…

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Locked on target

Posted on Mar 20th, 2020 - By Caitlin Deane

Nature Chemical Biology, Published online: 20 March 2020; doi:10.1038/s41589-020-0512-2Locked on…

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A gut reaction

Posted on Mar 20th, 2020 - By Mirella Bucci

Nature Chemical Biology, Published online: 20 March 2020; doi:10.1038/s41589-020-0514-0A gut…

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<span class=”small-caps”>d</span>-Cycloserine destruction by alanine racemase and the limit of irreversible inhibition

Posted on Mar 16th, 2020 - By Cesira de Chiara

Nature Chemical Biology, Published online: 16 March 2020; doi:10.1038/s41589-020-0498-9d-Cycloserine inactivates alanine racemase by forming an adduct with the pyridoxal 5′-phosphate cofactor, but structural and spectroscopic analyses reveal that reactivation occurs on adduct hydrolysis and product rearrangement to a stable…

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Atomic structure of potato virus X, the prototype of the <i>Alphaflexiviridae</i> family

Posted on Mar 16th, 2020 - By Alessandro Grinzato

Nature Chemical Biology, Published online: 16 March 2020; doi:10.1038/s41589-020-0502-4A cryo-EM structure of potato virus X shows that virions are formed by repeats of segments of coat protein protomers arranged in a left-handed helical structure and reveals details of the RNA–capsid interactions, which shed light on virus…

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A new path to tyrosine sulfation

Posted on Mar 16th, 2020 - By Chang C. Liu

Nature Chemical Biology, Published online: 16 March 2020; doi:10.1038/s41589-020-0482-4Tyrosine sulfation is a common post-translational modification known to play critical roles in multiple bioprocesses. A cleverly engineered mammalian expanded genetic code now enables the direct co-translational incorporation of tyrosine sulfates into proteins to study their function in cellular…

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A gene signal amplifier platform for monitoring the unfolded protein response

Posted on Mar 9th, 2020 - By Carlos A. Origel Marmolejo

Nature Chemical Biology, Published online: 09 March 2020; doi:10.1038/s41589-020-0497-xEngineering of a synthetic circuit that couples transcriptional and protein turnover regulation to a fluorescent protein readout enables sensitive monitoring and amplification of gene expression signals from the unfolded protein response…

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Activation of the α<sub>2B</sub> adrenoceptor by the sedative sympatholytic dexmedetomidine

Posted on Mar 9th, 2020 - By Daopeng Yuan

Nature Chemical Biology, Published online: 09 March 2020; doi:10.1038/s41589-020-0492-2A cryo-EM structure of the GPCR α2B adrenergic receptor (α2BAR) in complex with the selective agonist dexmedetomidine and the G protein Go suggests a mechanism of selective activation and provides insights into G-protein coupling…

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A bifunctional O-antigen polymerase structure reveals a new glycosyltransferase family

Posted on Mar 9th, 2020 - By Bradley R. Clarke

Nature Chemical Biology, Published online: 09 March 2020; doi:10.1038/s41589-020-0494-0Structural characterization of WbbM, an enzyme involved in O2a-antigen biosynthesis in Klebsiella pneumoniae, reveals two unique active sites with galactopyranosyl- or galactofuranosyl-transferase activities for oligosaccharide…

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A DNA-based fluorescent probe maps NOS3 activity with subcellular spatial resolution

Posted on Mar 9th, 2020 - By Maulik S. Jani

Nature Chemical Biology, Published online: 09 March 2020; doi:10.1038/s41589-020-0491-3A pair of fluorescent DNA-based probes for nitric oxide reveals that nitric oxide synthase 3 activity in the trans-Golgi network is essential for Golgi structural integrity, despite being tenfold less active there than at the plasma…

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Paradoxical mitotic exit induced by a small molecule inhibitor of APC/C<sup>Cdc20</sup>

Posted on Mar 9th, 2020 - By Katherine V. Richeson

Nature Chemical Biology, Published online: 09 March 2020; doi:10.1038/s41589-020-0495-zA small-molecule ligand of the APC/C activator Cdc20, which prolongs mitosis in unperturbed cells, instead shortens mitosis when the spindle checkpoint is activated, producing an opposite effect in a different regulatory…

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Hitchhiking into the cell

Posted on Mar 9th, 2020 - By Douglas B. Kell

Nature Chemical Biology, Published online: 09 March 2020; doi:10.1038/s41589-020-0489-xThe mechanisms by which bioactive drugs get into their target cells is a question that has been greatly neglected. A new survey with CRISPR–Cas9 shows the widespread importance of protein transporters called solute carriers…

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A widespread role for SLC transmembrane transporters in resistance to cytotoxic drugs

Posted on Mar 9th, 2020 - By Enrico Girardi

Nature Chemical Biology, Published online: 09 March 2020; doi:10.1038/s41589-020-0483-3A set of CRISPR–Cas9-based genetic screens in a haploid human cell line identifies more than 200 gene–drug associations involving solute carriers (SLCs), transporters important for the uptake and activity of cytotoxic…

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Deep mutational scanning reveals the structural basis for α-synuclein activity

Posted on Mar 9th, 2020 - By Robert W. Newberry

Nature Chemical Biology, Published online: 09 March 2020; doi:10.1038/s41589-020-0480-6Deep mutational scanning reveals that α-synuclein adopts a membrane-bound α-helix conformation with increasing dynamics towards the C terminus. This helical conformation is associated with its…

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A drug discovery platform to identify compounds that inhibit EGFR triple mutants

Posted on Feb 24th, 2020 - By Punit Saraon

Nature Chemical Biology, Published online: 24 February 2020; doi:10.1038/s41589-020-0484-2A high-throughput small-molecule drug screening platform enabled the detection of compounds targeting the functional interactions of receptor tyrosine kinases and identifies four new EGFR triple-mutant…

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Endosome motility defects revealed at super-resolution in live cells using HIDE probes

Posted on Feb 24th, 2020 - By Aarushi Gupta

Nature Chemical Biology, Published online: 24 February 2020; doi:10.1038/s41589-020-0479-zHIDE probes were developed for long time-lapse imaging of endolysosomes and their dynamics at super-resolution. These probes enabled analyses of endosome motility in primary fibroblasts from patients with Niemann–Pick C with distinct mutations in…

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Restoring the balance

Posted on Feb 20th, 2020 - By Caitlin Deane

Nature Chemical Biology, Published online: 20 February 2020; doi:10.1038/s41589-020-0485-1Restoring the…

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Investigating PIs

Posted on Feb 20th, 2020 - By Mirella Bucci

Nature Chemical Biology, Published online: 20 February 2020; doi:10.1038/s41589-020-0487-zInvestigating…

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Biased M1-muscarinic-receptor-mutant mice inform the design of next-generation drugs

Posted on Feb 20th, 2020 - By Sophie J. Bradley

Nature Chemical Biology, Published online: 20 February 2020; doi:10.1038/s41589-019-0453-9Use of receptor variants in knock-in mice to dissect phosphorylation-dependent signaling from G protein-dependent signaling mediated by acetylcholine receptor M1 mAChR defines the ability of receptor ligands to modulate anxiety and locomotion…

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Leveraging bias to your advantage

Posted on Feb 20th, 2020 - By Sean P. Moran

Nature Chemical Biology, Published online: 20 February 2020; doi:10.1038/s41589-020-0468-2Characterization of biased receptor signaling has ushered in opportunities for unprecedented control of G-protein-coupled receptors. Elucidation of distinct M1 muscarinic acetylcholine receptor signaling pathways and development of biased ligands may offer novel and safer Alzheimer’s disease…

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Cryo-electron microscopy for the study of virus assembly

Posted on Feb 20th, 2020 - By Daniel Luque

Nature Chemical Biology, Published online: 20 February 2020; doi:10.1038/s41589-020-0477-1Cryo-EM and Cryo-ET have emerged as useful tools to study the efficient and dynamic processes of the viral…

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Hooked on vitamins

Posted on Feb 20th, 2020 - By Grant Miura

Nature Chemical Biology, Published online: 20 February 2020; doi:10.1038/s41589-020-0486-0Hooked on…

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A stop to signaling

Posted on Feb 20th, 2020 - By Yiyun Song

Nature Chemical Biology, Published online: 20 February 2020; doi:10.1038/s41589-020-0488-yA stop to…

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Rendezvous of Retro-2 at the ER

Posted on Feb 17th, 2020 - By Hesso Farhan

Nature Chemical Biology, Published online: 17 February 2020; doi:10.1038/s41589-020-0475-3Retro-2 is a drug that protects cells against bacterial and plant toxins by arresting their trafficking in endosomes. New data show that the target for Retro-2 is surprisingly not within the endosomal system, but on the endoplasmic…

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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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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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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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