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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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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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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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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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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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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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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<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 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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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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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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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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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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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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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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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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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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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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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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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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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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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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