Toward spatially resolved metabolomics

Posted on Sep 17th, 2020 - By Bennett W. Fox

Nature Chemical Biology, Published online: 17 September 2020; doi:10.1038/s41589-020-00650-0Coherent Raman imaging enables mapping of chemical features at subcellular resolution, setting the stage for tracking lipids and other metabolites in intact living…

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Made fresh in-house

Posted on Sep 17th, 2020 - By Yiyun Song

Nature Chemical Biology, Published online: 17 September 2020; doi:10.1038/s41589-020-00664-8Made fresh…

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Three’s company

Posted on Sep 17th, 2020 - By Caitlin Deane

Nature Chemical Biology, Published online: 17 September 2020; doi:10.1038/s41589-020-00661-xThree’s…

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Importin pain relief

Posted on Sep 17th, 2020 - By Mirella Bucci

Nature Chemical Biology, Published online: 17 September 2020; doi:10.1038/s41589-020-00663-9Importin pain…

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Bacterial virulence mediated by orthogonal post-translational modification

Posted on Sep 17th, 2020 - By Kaitlin A. Chambers

Nature Chemical Biology, Published online: 17 September 2020; doi:10.1038/s41589-020-0638-2Virulence factors from various bacterial pathogens catalyze post-translational modification of key host proteins, including phosphate β-elimination and phosphoribosyl-linked ubiquitination, to suppress host immune defenses and promote…

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Uncovering nature’s electronics

Posted on Sep 17th, 2020 - By Thomas A. Clarke

Nature Chemical Biology, Published online: 17 September 2020; doi:10.1038/s41589-020-00655-9The electrogenic bacterium Geobacter synthesizes conductive extracellular nanowires to facilitate electron transfer that powers respiration. A highly conductive form of these nanowires is now revealed to be composed of oligomers of an 8-heme cytochrome,…

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Shifting the balance

Posted on Sep 17th, 2020 - By Grant Miura

Nature Chemical Biology, Published online: 17 September 2020; doi:10.1038/s41589-020-00662-wShifting the…

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MYPT1 <i>O</i>-GlcNAc modification regulates sphingosine-1-phosphate mediated contraction

Posted on Sep 14th, 2020 - By Nichole J. Pedowitz

Nature Chemical Biology, Published online: 14 September 2020; doi:10.1038/s41589-020-0640-8Changes in O-GlcNAc levels controlled the actin contraction of fibroblasts in response to sphingosine-1-phosphate (S1P). Specifically, O-GlcNAc modification of the phosphatase MYPT1 maintains its activity to block S1P…

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Covalent inhibition of NSD1 histone methyltransferase

Posted on Aug 31st, 2020 - By Huang Huang

Nature Chemical Biology, Published online: 31 August 2020; doi:10.1038/s41589-020-0626-6An irreversible small-molecule inhibitor of histone methyltransferase NSD1 is developed, which binds covalently to the C2062 residue in the catalytic SET domain and represses H3K36 dimethylation and target gene expression in leukemia…

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Bariatric surgery works through a novel bile acid

Posted on Aug 26th, 2020 - By Bethany P. Cummings

Nature Chemical Biology, Published online: 26 August 2020; doi:10.1038/s41589-020-0648-0Bariatric surgery causes high rates of remission of type 2 diabetes; however, the mechanisms remain unresolved. A new study identifies cholic-acid-7-sulfate as a novel contributor to the metabolic benefits of bariatric surgery and an attractive target for treatment of type 2…

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Structural basis for antibiotic action of the B<sub>1</sub> antivitamin 2′-methoxy-thiamine

Posted on Aug 24th, 2020 - By Fabian Rabe von Pappenheim

Nature Chemical Biology, Published online: 24 August 2020; doi:10.1038/s41589-020-0628-4Structural and biochemical analysis of E. coli transketolase with 2′-methoxy-thiamine shows that this antivitamin selectively inhibits the bacterial enzyme via a steric clash with a critical glutamate residue, preventing cofactor…

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A bio-inspired cell-free system for cannabinoid production from inexpensive inputs

Posted on Aug 24th, 2020 - By Meaghan A. Valliere

Nature Chemical Biology, Published online: 24 August 2020; doi:10.1038/s41589-020-0631-9A cell-free system for cannabinoid production uses only low-cost inputs with 12 enzymes and can operate either aerobically or anaerobically, in addition to reducing ATP requirements by use of an engineered system for malonate-CoA…

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Peaking at the right time

Posted on Aug 18th, 2020 - By Grant Miura

Nature Chemical Biology, Published online: 18 August 2020; doi:10.1038/s41589-020-0634-6Peaking at the right…

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Repair switches

Posted on Aug 18th, 2020 - By Yiyun Song

Nature Chemical Biology, Published online: 18 August 2020; doi:10.1038/s41589-020-0636-4Repair…

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Histones do double duty

Posted on Aug 18th, 2020 - By Caitlin Deane

Nature Chemical Biology, Published online: 18 August 2020; doi:10.1038/s41589-020-0633-7Histones do double…

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Channeling a complex question

Posted on Aug 18th, 2020 - By Martin St. Maurice

Nature Chemical Biology, Published online: 18 August 2020; doi:10.1038/s41589-020-0619-5It is generally believed that large protein complexes provide a catalytic advantage due to substrate channeling between enzymatic domains. However, the structure and function of the pentafunctional AROM complex suggests a noteworthy…

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Modulating the microbiota

Posted on Aug 18th, 2020 - By Mirella Bucci

Nature Chemical Biology, Published online: 18 August 2020; doi:10.1038/s41589-020-0635-5Modulating the…

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Electric field stimulates production of highly conductive microbial OmcZ nanowires

Posted on Aug 17th, 2020 - By Sibel Ebru Yalcin

Nature Chemical Biology, Published online: 17 August 2020; doi:10.1038/s41589-020-0623-9Application of an electrical field to Geobacter sulfurreducens biofilms stimulates production of OmcZ nanowires, which undergo a pH-induced conformational switch that causes increased stiffness and conductivity due to enhanced heme group…

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Publisher Correction: A mass spectrometry-based proteome map of drug action in lung cancer cell lines

Posted on Aug 11th, 2020 - By Benjamin Ruprecht

Nature Chemical Biology, Published online: 11 August 2020; doi:10.1038/s41589-020-0643-5Publisher Correction: A mass spectrometry-based proteome map of drug action in lung cancer cell…

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Functional characterization of a PROTAC directed against BRAF mutant V600E

Posted on Aug 10th, 2020 - By Ganna Posternak

Nature Chemical Biology, Published online: 10 August 2020; doi:10.1038/s41589-020-0609-7A PROTAC termed P4B targeting BRAF V600E mutant has been developed, which displays enhanced inhibitory function in cell lines carrying BRAF mutations that impart resistance to conventional BRAF…

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Active turnover of genomic methylcytosine in pluripotent cells

Posted on Aug 10th, 2020 - By Fabio Spada

Nature Chemical Biology, Published online: 10 August 2020; doi:10.1038/s41589-020-0621-yThe combination of heavy isotope labeling and ultra-high-pressure liquid chromatography coupled to triple-quadrupole mass spectrometry (UHPLC–MS) is used to quantify modified genomic cytosines in pluripotent stem cells in different states and reveals active turnover of methylcytidine in oxidation-dependent and oxidation-independent…

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A bioluminescent probe for longitudinal monitoring of mitochondrial membrane potential

Posted on Aug 10th, 2020 - By Arkadiy A. Bazhin

Nature Chemical Biology, Published online: 10 August 2020; doi:10.1038/s41589-020-0602-1A mitochondria-activatable bioluminescent probe was designed enabling sensitive, non-invasive and longitudinal monitoring of mitochondrial membrane potential in vitro and in…

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G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3

Posted on Aug 10th, 2020 - By Signe Mathiasen

Nature Chemical Biology, Published online: 10 August 2020; doi:10.1038/s41589-020-0617-7Among the adhesion receptor class of GPCRs, which are understudied, the adhesion receptor ADGRL3 can be activated by its own tethered agonist and couples to G protein G12/13 and somewhat to…

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Orthogonal fluorescent chemogenetic reporters for multicolor imaging

Posted on Aug 10th, 2020 - By Alison G. Tebo

Nature Chemical Biology, Published online: 10 August 2020; doi:10.1038/s41589-020-0611-0The fluorescent chemogenetic reporters greenFAST and redFAST were engineered by protein engineering. They display orthogonal fluorogen recognition and spectral properties allowing efficient multicolor imaging of proteins in live cells and…

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Metabolic determinants of cancer cell sensitivity to canonical ferroptosis inducers

Posted on Aug 10th, 2020 - By Mariluz Soula

Nature Chemical Biology, Published online: 10 August 2020; doi:10.1038/s41589-020-0613-yGenetic screens reveal a compendium of metabolic modifiers of lipid peroxidation. Tetrahydrobiopterin is essential under GPX4 inhibition, acting as a radical-trapping antioxidant that inhibits lipid peroxidation and is regenerated by…

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Prospecting for molecular glues

Posted on Aug 3rd, 2020 - By Willem den Besten

Nature Chemical Biology, Published online: 03 August 2020; doi:10.1038/s41589-020-0620-zTwo recent studies identified CDK12 inhibitors that bind to CDK12–cyclin K complexes and act as molecular glues to stabilize an interaction with the ubiquitin ligase CUL4–DDB1, leading to cyclin K…

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Enzymatic C–H activation of aromatic compounds through CO<sub>2</sub> fixation

Posted on Jul 27th, 2020 - By Godwin A. Aleku

Nature Chemical Biology, Published online: 27 July 2020; doi:10.1038/s41589-020-0603-0Biocatalytic cascade reactions using engineered variants of ferulic acid decarboxylase coupled to carboxylic acid reductase utilize carbon dioxide fixation to enable the carboxylation and functionalization of styrene and other aromatic…

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p63 uses a switch-like mechanism to set the threshold for induction of apoptosis

Posted on Jul 27th, 2020 - By Jakob Gebel

Nature Chemical Biology, Published online: 27 July 2020; doi:10.1038/s41589-020-0600-3TAp63α monitors the genome integrity in oocytes. After DNA damage, TAp63α is activated, involving multiple phosphorylation steps by CK1 with different kinetics due to an unusual CK1/TAp63α interaction in which the product of one step inhibits the…

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Engineering orthogonal human <i>O-</i>linked glycoprotein biosynthesis in bacteria

Posted on Jul 27th, 2020 - By Aravind Natarajan

Nature Chemical Biology, Published online: 27 July 2020; doi:10.1038/s41589-020-0595-9An orthogonal O-glycan biosynthesis system was engineered in Escherichia coli to support the production of glycoproteins displaying human mucin O-glycans, including Tn antigens, in living bacteria and in cell-free…

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NADP modulates RNA m<sup>6</sup>A methylation and adipogenesis via enhancing FTO activity

Posted on Jul 27th, 2020 - By Lina Wang

Nature Chemical Biology, Published online: 27 July 2020; doi:10.1038/s41589-020-0601-2NADP can directly bind with FTO and enhance its m6A demethylase activity, thus affecting RNA m6A modification and…

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Living cells as test tubes

Posted on Jul 24th, 2020 - By Roshan Mammen Regy

Nature Chemical Biology, Published online: 24 July 2020; doi:10.1038/s41589-020-0615-9Thermodynamic principles are used to map the phase behavior of a tunable protein-binding system under crowded cellular conditions. This study marks a substantial step forward in relating molecular interactions to material properties and cellular processes involving protein…

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A stress-free stress response

Posted on Jul 23rd, 2020 - By Nadia Cummins

Nature Chemical Biology, Published online: 23 July 2020; doi:10.1038/s41589-020-0616-8A new molecule that specifically activates a key protein homeostasis pathway has been identified. The ability to initiate the IRE1–XBP1s branch of the unfolded protein response opens up new avenues for basic research and treatment of…

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Publisher Correction: Acoustic biosensors for ultrasound imaging of enzyme activity

Posted on Jul 23rd, 2020 - By Anupama Lakshmanan

Nature Chemical Biology, Published online: 23 July 2020; doi:10.1038/s41589-020-0630-xPublisher Correction: Acoustic biosensors for ultrasound imaging of enzyme…

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A sensory override

Posted on Jul 21st, 2020 - By Mirella Bucci

Nature Chemical Biology, Published online: 21 July 2020; doi:10.1038/s41589-020-0607-9A sensory…

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Author Correction: The bottromycin epimerase BotH defines a group of atypical α/β-hydrolase-fold enzymes

Posted on Jul 15th, 2020 - By Asfandyar Sikandar

Nature Chemical Biology, Published online: 15 July 2020; doi:10.1038/s41589-020-0624-8Author Correction: The bottromycin epimerase BotH defines a group of atypical α/β-hydrolase-fold…

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Expanding the membrane-protein NMR toolkit

Posted on Jul 14th, 2020 - By Ricky C. Cheng

Nature Chemical Biology, Published online: 14 July 2020; doi:10.1038/s41589-020-0597-7An NMR method to monitor conformational states of challenging large protein targets is described. The method, which can be used to evaluate distances between two labels and to measure conformational exchange rates, revealed an unanticipated outward-facing state in a glutamate…

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Designer protein assemblies with tunable phase diagrams in living cells

Posted on Jul 13th, 2020 - By Meta Heidenreich

Nature Chemical Biology, Published online: 13 July 2020; doi:10.1038/s41589-020-0576-zA synthetic phase separation system consisting of two protein components with tunable parameters was developed to visualize and characterize phase diagrams in living cells, revealing that increasing the interaction affinity enhances phase separation and the viscosity of condensates in…

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Acoustic biosensors for ultrasound imaging of enzyme activity

Posted on Jul 13th, 2020 - By Anupama Lakshmanan

Nature Chemical Biology, Published online: 13 July 2020; doi:10.1038/s41589-020-0591-0Engineering cleavage sites into gas vesicle proteins enables protease-responsive regulation of gas vesicle mechanics and activates them as ultrasound contrast agents for imaging applications in cells and living…

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A quantitative method for proteome reallocation using minimal regulatory interventions

Posted on Jul 13th, 2020 - By Gustavo Lastiri-Pancardo

Nature Chemical Biology, Published online: 13 July 2020; doi:10.1038/s41589-020-0593-yAn econometric model built on regulatory networks and calibrated by proteomics data identifies nonessential transcription factors that when deleted in Escherichia coli result in a strain with an expanded proteome for engineering…

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Allosteric interactions in the parathyroid hormone GPCR–arrestin complex formation

Posted on Jul 6th, 2020 - By Lisa J. Clark

Nature Chemical Biology, Published online: 06 July 2020; doi:10.1038/s41589-020-0567-0Characterization of the interaction between PTH and its G-protein-coupled receptor, PTHR, shows conformational changes coupled to residues interacting with His9, which helps position the PTH N terminus at the PTHR transmembrane domain to facilitate β-arrestin…

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Architecture and functional dynamics of the pentafunctional AROM complex

Posted on Jul 6th, 2020 - By Harshul Arora Verasztó

Nature Chemical Biology, Published online: 06 July 2020; doi:10.1038/s41589-020-0587-9Structural, conformational and biochemical characterization of the AROM complex and its constituent shikimate pathway domains reveals how the complex balances compactness and conformational freedom, yet does not benefit from substrate…

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Formation and functionalization of membraneless compartments in <i>Escherichia coli</i>

Posted on Jun 29th, 2020 - By Shao-Peng Wei

Nature Chemical Biology, Published online: 29 June 2020; doi:10.1038/s41589-020-0579-9Utilization of structural proteins with intrinsically disordered regions enables the formation of membraneless organelles in Escherichia coli through liquid–liquid phase separation, as well as their functionalization with active…

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The bottromycin epimerase BotH defines a group of atypical α/β-hydrolase-fold enzymes

Posted on Jun 29th, 2020 - By Asfandyar Sikandar

Nature Chemical Biology, Published online: 29 June 2020; doi:10.1038/s41589-020-0569-yBotH is an unusual α/β-hydrolase-fold enzyme that catalyzes epimerization of an aspartate residue during bottromycin biosynthesis via a mechanism distinct from other known peptide natural product…

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Tetracenomycin X inhibits translation by binding within the ribosomal exit tunnel

Posted on Jun 29th, 2020 - By Ilya A. Osterman

Nature Chemical Biology, Published online: 29 June 2020; doi:10.1038/s41589-020-0578-xStructural and biochemical analysis reveal that tetracenomycin X acts as an inhibitor of protein synthesis by binding within the exit tunnel in a large ribosomal unit to prevent the prolongation of the nascent polypeptide…

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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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