Cryptic phosphorylation in nucleoside natural product biosynthesis

Posted on Nov 30th, 2020 - By Matthew M. Draelos

Nature Chemical Biology, Published online: 30 November 2020; doi:10.1038/s41589-020-00656-8Rather than their expected role in self-immunity, kinases encoded in the biosynthetic gene clusters of nucleoside natural products catalyze the phosphorylation of an early intermediate, a modification that is later removed in a downstream…

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Ion channels as lipid sensors: from structures to mechanisms

Posted on Nov 16th, 2020 - By Mackenzie J. Thompson

Nature Chemical Biology, Published online: 16 November 2020; doi:10.1038/s41589-020-00693-3Ion channel structures reveal mechanisms of lipid action, including how channel gating is altered by direct binding of signaling lipids and those within the membrane itself, as well as mechanical and architectural effects of membrane…

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Cell type-selective secretome profiling in vivo

Posted on Nov 16th, 2020 - By Wei Wei

Nature Chemical Biology, Published online: 16 November 2020; doi:10.1038/s41589-020-00698-yA proximity labeling strategy enables enrichment of cell type-selective secretomes in mice by direct biochemical purification of biotinylated polypeptides from blood…

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Defining new chemical space for drug penetration into Gram-negative bacteria

Posted on Nov 16th, 2020 - By Shibin Zhao

Nature Chemical Biology, Published online: 16 November 2020; doi:10.1038/s41589-020-00674-6The difficulty of antibiotic discovery posed by the double-membrane cell envelope of Gram-negative bacteria and active drug efflux requires better understanding of bacterial permeability and compound accumulation, and more diverse chemical…

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Snapshots and ensembles of BTK and cIAP1 protein degrader ternary complexes

Posted on Nov 16th, 2020 - By James Schiemer

Nature Chemical Biology, Published online: 16 November 2020; doi:10.1038/s41589-020-00686-2The authors report PROTAC ternary complex structures involving the E3 ligase cIAP1 and target protein BTK, showing that cooperativity is not always correlated with degradation…

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The conformational cycle of a prototypical voltage-gated sodium channel

Posted on Nov 16th, 2020 - By William A. Catterall

Nature Chemical Biology, Published online: 16 November 2020; doi:10.1038/s41589-020-0644-4The conformational cycle of a bacterial voltage-gated sodium channel as it transitions from resting to activated open to inactivated closed states can be constructed from various crystal structure…

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Delimiting lipids

Nature Chemical Biology, Published online: 16 November 2020; doi:10.1038/s41589-020-00701-6This themed issue features a collection of articles that explore long-standing questions in the study of lipids and…

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Making use of surplus sugar

Posted on Nov 16th, 2020 - By Niels Agerbirk

Nature Chemical Biology, Published online: 16 November 2020; doi:10.1038/s41589-020-00687-1Insects have many ways of disabling plant chemical defenses during feeding. Plant phloem feeders use surplus ingested sugar to block the activation of glucosinolate toxins, providing a target for precise resistance…

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Chemically informed analyses of metabolomics mass spectrometry data with Qemistree

Posted on Nov 16th, 2020 - By Anupriya Tripathi

Nature Chemical Biology, Published online: 16 November 2020; doi:10.1038/s41589-020-00677-3Qemistree uses fragmentation spectra to predict molecular fingerprints and represent their relationships as a tree, enabling comparison of metabolomics data across different experimental conditions and exploration of chemical diversity in…

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Chemical reversal of abnormalities in cells carrying mitochondrial DNA mutations

Posted on Nov 9th, 2020 - By Hiroki Kobayashi

Nature Chemical Biology, Published online: 09 November 2020; doi:10.1038/s41589-020-00676-4Tryptolinamide (TLAM) is a small molecule compound that inhibits phosphofructokinase-1 activity and rescues the metabolic defects of patient-derived induced pluripotent stem cell lines with mutated mitochondrial…

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Production of Tyrian purple indigoid dye from tryptophan in <i>Escherichia coli</i>

Posted on Nov 2nd, 2020 - By Jeongchan Lee

Nature Chemical Biology, Published online: 02 November 2020; doi:10.1038/s41589-020-00684-4A two-cell setup containing tryptophanase, a flavin-dependent monooxygenase and a regiospecific halogenase (linked to a flavin reductase as a solubility tag) enables the production of 6,6'-dibromoindigo and other indigoid dyes in Escherichia…

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Synthetic yeast brews neuroactive compounds

Posted on Oct 28th, 2020 - By Yang Gu

Nature Chemical Biology, Published online: 28 October 2020; doi:10.1038/s41589-020-00691-5Metabolic engineering offers the flexibility to meet market demand for bioactive natural products but can be hampered when a necessary protein or intermediate is toxic. In yeast, modifying the subcellular localization of biosynthetic enzymes can alleviate toxicity and increase production…

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Structural basis for persulfide-sensing specificity in a transcriptional regulator

Posted on Oct 26th, 2020 - By Daiana A. Capdevila

Nature Chemical Biology, Published online: 26 October 2020; doi:10.1038/s41589-020-00671-9Structural and kinetic analyses of the transcriptional repressor SqrR in multiple states indicate that its persulfide selectivity is determined by structural frustration in the disulfide form, favoring formation of the tetrasulfide-bridged…

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Rerouting plant terpene biosynthesis enables momilactone pathway elucidation

Posted on Oct 26th, 2020 - By Ricardo De La Peña

Nature Chemical Biology, Published online: 26 October 2020; doi:10.1038/s41589-020-00669-3Redirecting plant diterpene biosynthesis from the chloroplast to the cytosolic, high-flux mevalonate pathway increases intermediate and product titers to support the elucidation and reconstitution of momilactone…

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Interhelical interactions within the STIM1 CC1 domain modulate CRAC channel activation

Posted on Oct 26th, 2020 - By Petr Rathner

Nature Chemical Biology, Published online: 26 October 2020; doi:10.1038/s41589-020-00672-8The helical bundle structure of the CC1 domain of STIM1 of the store-activated calcium channel CRAC is crucial to maintaining the channel resting state, and helix–helix interactions can be manipulated to normalize a disease-linked STIM1…

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Visualizing a protonated RNA state that modulates microRNA-21 maturation

Posted on Oct 26th, 2020 - By Jared T. Baisden

Nature Chemical Biology, Published online: 26 October 2020; doi:10.1038/s41589-020-00667-5The authors identified a pH-dependent protonated status in the miR-21 precursor, which leads to additional base pairing in its secondary structure, thus affecting Dicer processing and miR-21…

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SARS-CoV-2 M<sup>pro</sup> inhibitors and activity-based probes for patient-sample imaging

Posted on Oct 22nd, 2020 - By Wioletta Rut

Nature Chemical Biology, Published online: 22 October 2020; doi:10.1038/s41589-020-00689-zScreening for substrate preference of the SARS-CoV and SARS-CoV-2 main protease Mpro leads to the development of activity-based probes useful for structural analysis and for visualization of active Mpro in infected patient epithelial…

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Bi-paratopic and multivalent VH domains block ACE2 binding and neutralize SARS-CoV-2

Posted on Oct 20th, 2020 - By Colton J. Bracken

Nature Chemical Biology, Published online: 20 October 2020; doi:10.1038/s41589-020-00679-1A screening approach finds VH-domain antibodies that bind the SARS-CoV-2 Spike protein receptor-binding domain at its interface with host ACE2. Bi-paratopic and multivalent binders have high affinity and…

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Cuticle thickness affects dynamics of volatile emission from petunia flowers

Posted on Oct 19th, 2020 - By Pan Liao

Nature Chemical Biology, Published online: 19 October 2020; doi:10.1038/s41589-020-00670-wThe plant cuticle was initially thought to act as a passive diffusion barrier. Genetic and metabolic analysis reveals that it is also a sink/concentrator for volatiles protecting cells from toxic effects of these hydrophobic…

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Launching the missile

Posted on Oct 16th, 2020 - By Yiyun Song

Nature Chemical Biology, Published online: 16 October 2020; doi:10.1038/s41589-020-00683-5Launching the…

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It’s a trap!

Posted on Oct 16th, 2020 - By Caitlin Deane

Nature Chemical Biology, Published online: 16 October 2020; doi:10.1038/s41589-020-00680-8It’s a…

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Advanced rules of relays

Posted on Oct 16th, 2020 - By Sonja Lorenz

Nature Chemical Biology, Published online: 16 October 2020; doi:10.1038/s41589-020-0632-8Transfer of ubiquitin onto target proteins requires controlled interplay between E2 conjugating enzymes and E3 ligases. The structure of a trapped E2~Ub/RCR E3 transfer intermediate provides novel insight into the diversity of mechanisms used to fine tune this…

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Hijacking protein degradation

Nature Chemical Biology, Published online: 16 October 2020; doi:10.1038/s41589-020-00685-3Targeted protein degradation provides a powerful complement to small-molecule inhibition in modulating protein activity and allows access to otherwise intractable drug…

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Clarifying the translational potential of B-I09

Posted on Oct 16th, 2020 - By Juan R. Del Valle

Nature Chemical Biology, Published online: 16 October 2020; doi:10.1038/s41589-020-00654-wClarifying the translational potential of…

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Kinase ins and outs

Posted on Oct 16th, 2020 - By Mirella Bucci

Nature Chemical Biology, Published online: 16 October 2020; doi:10.1038/s41589-020-00682-6Kinase ins and…

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Reversal of nucleobase methylation by dioxygenases

Posted on Oct 16th, 2020 - By Guo-Liang Xu

Nature Chemical Biology, Published online: 16 October 2020; doi:10.1038/s41589-020-00675-5This Review summarizes the chemical and physical properties of methylated nucleobases in DNA and RNA, proposes a chemical classification of methylation types, and discusses recent advance in demethylation reactions mediated by…

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Fine-tuning adhesives

Posted on Oct 16th, 2020 - By Grant Miura

Nature Chemical Biology, Published online: 16 October 2020; doi:10.1038/s41589-020-00681-7Fine-tuning…

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Peroxisome compartmentalization of a toxic enzyme improves alkaloid production

Posted on Oct 12th, 2020 - By Parbir S. Grewal

Nature Chemical Biology, Published online: 12 October 2020; doi:10.1038/s41589-020-00668-4Increased production of (S)-reticuline and other alkaloids is achieved through alleviating norcoclaurine synthase toxicity by targeting the enzyme to the peroxisome plus enlarging peroxisomes by expression of engineered transcription…

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Discovery of iron-sensing bacterial riboswitches

Posted on Oct 5th, 2020 - By Siladitya Bandyopadhyay

Nature Chemical Biology, Published online: 05 October 2020; doi:10.1038/s41589-020-00665-7A family of riboswitches named Sensei that specifically sense iron has been discovered and characterized, which enables the authors to engineer metal ion sensing riboswitches to convert their metal…

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Sulfated glycans engage the Ang–Tie pathway to regulate vascular development

Posted on Oct 5th, 2020 - By Matthew E. Griffin

Nature Chemical Biology, Published online: 05 October 2020; doi:10.1038/s41589-020-00657-7A chemical glycobiology approach reveals that heparan-sulfate glycosaminoglycans regulate vascular development through direct interactions with angiopoietin (Ang) ligands and the Tie1 receptor of the Ang–Tie signaling…

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PROTAC-mediated degradation reveals a non-catalytic function of AURORA-A kinase

Posted on Sep 28th, 2020 - By Bikash Adhikari

Nature Chemical Biology, Published online: 28 September 2020; doi:10.1038/s41589-020-00652-yA bifunctional AURORA-A degrader induces the fast and specific degradation of this kinase in cancer cell lines, which enables targeting of non-catalytic, oncogenic functions of AURORA-A resulting in S-phase arrest and rampant…

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Designer adhesion GPCR tells its signaling story

Posted on Sep 28th, 2020 - By Eugenia V. Gurevich

Nature Chemical Biology, Published online: 28 September 2020; doi:10.1038/s41589-020-00673-7The ADGRL3 receptor, a member of the adhesion G-protein-coupled receptor family, is implicated in many neurological diseases. Using a novel technique involving controlled proteolysis of the receptor’s extracellular domain, this study demonstrated that ADGRL3 signals via G12/13 G…

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Selective regulation of human TRAAK channels by biologically active phospholipids

Posted on Sep 28th, 2020 - By Samantha Schrecke

Nature Chemical Biology, Published online: 28 September 2020; doi:10.1038/s41589-020-00659-5Native ion mobility mass spectrometry reveals two isoforms of the two-pore domain K+ channel K2P4.1 have distinct binding preferences for lipids and show a relationship between the strength of individual lipid binding events and channel…

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An ultrasensitive biosensor for high-resolution kinase activity imaging in awake mice

Posted on Sep 28th, 2020 - By Jin-Fan Zhang

Nature Chemical Biology, Published online: 28 September 2020; doi:10.1038/s41589-020-00660-yA fluorescence-based sensor of PKA activity has increased brightness, dynamic range and signal-to-noise ratio over related sensors and is useful for visualizing kinase activity in HeLa cells, primary neurons and the cortex of awake…

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Glucosylation prevents plant defense activation in phloem-feeding insects

Posted on Sep 28th, 2020 - By Osnat Malka

Nature Chemical Biology, Published online: 28 September 2020; doi:10.1038/s41589-020-00658-6The whitefly Bemisia tabaci defends against plant glucosinolate toxins by serial addition of glucose moieties catalyzed by a pair of glycoside hydrolases, preventing toxin activation during feeding on the plant…

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CueR activates transcription through a DNA distortion mechanism

Posted on Sep 28th, 2020 - By Chengli Fang

Nature Chemical Biology, Published online: 28 September 2020; doi:10.1038/s41589-020-00653-xStructural analysis of transcription activation complex comprising E. coli transcription factor CueR, RNAP holoenzyme and promoter DNA reveals that CueR distorts the DNA conformation to promote the association of promoter with…

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Organelle membrane-specific chemical labeling and dynamic imaging in living cells

Posted on Sep 21st, 2020 - By Tomonori Tamura

Nature Chemical Biology, Published online: 21 September 2020; doi:10.1038/s41589-020-00651-zImaging of phosphatidylcholine, sphingomyelin and their interorganelle lipid transport in live cells, using azido-choline and a spatially limited bioorthogonal tag, suggests that autophagosomal membranes originate from the…

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ARID2 is a pomalidomide-dependent CRL4<sup>CRBN</sup> substrate in multiple myeloma cells

Posted on Sep 21st, 2020 - By Junichi Yamamoto

Nature Chemical Biology, Published online: 21 September 2020; doi:10.1038/s41589-020-0645-3Immunomodulatory drugs are used for the treatment of multiple myeloma. ARID2, a component of the PBAF chromatin-remodeling complex, is a new pomalidomide-induced neosubstrate of CRL4CRBN, which accounts for its superior efficacy over…

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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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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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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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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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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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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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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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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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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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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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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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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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