Lanthanide lover

Posted on Dec 10th, 2018 - By Caitlin Deane

Lanthanide loverLanthanide lover, Published online: 10 December 2018; doi:10.1038/s41589-018-0196-zLanthanide…

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E2 enzymes: lessons in ubiquitin transfer from XLID patients

Posted on Dec 10th, 2018 - By Martina Foglizzo

E2 enzymes: lessons in ubiquitin transfer from XLID patientsE2 enzymes: lessons in ubiquitin transfer from XLID patients, Published online: 10 December 2018; doi:10.1038/s41589-018-0191-4Characterization of a novel mutation in the E2 ubiquitin-conjugating enzyme UBE2A accounts for the decreased activity of the mutant enzyme that underlies disease and provides important insight into the catalytic mechanism of…

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Mechanistic insights revealed by a UBE2A mutation linked to intellectual disability

Posted on Dec 10th, 2018 - By Juliana Ferreira de Oliveira

Mechanistic insights revealed by a UBE2A mutation linked to intellectual disabilityMechanistic insights revealed by a UBE2A mutation linked to intellectual disability, Published online: 10 December 2018; doi:10.1038/s41589-018-0177-2Structural and biochemical analysis of a UBE2A mutation linked to intellectual disability reveals that the Q93E mutant perturbs the E2 catalytic microenvironment essential for lysine deprotonation during the ubiquitin-transfer…

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<i>N</i><sup>6</sup>-mA condenses chromatin

Posted on Dec 10th, 2018 - By Yiyun Song

N6-mA condenses chromatin<i>N</i><sup>6</sup>-mA condenses chromatin, Published online: 10 December 2018; doi:10.1038/s41589-018-0199-9N6-mA condenses…

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Riboregulated toehold-gated gRNA for programmable CRISPR–Cas9 function

Posted on Dec 10th, 2018 - By Ka-Hei Siu

Riboregulated toehold-gated gRNA for programmable CRISPR–Cas9 functionRiboregulated toehold-gated gRNA for programmable CRISPR–Cas9 function, Published online: 10 December 2018; doi:10.1038/s41589-018-0186-1Engineering of toehold-gated guide RNA (thgRNA) by tethering toehold riboswitches to sgRNAs enables the activation of CRISPR–Cas9 genome editing or transcriptional regulation in response to complementary synthetic or endogenous cellular…

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The bacteria that move me

Posted on Dec 10th, 2018 - By Mirella Bucci

The bacteria that move meThe bacteria that move me, Published online: 10 December 2018; doi:10.1038/s41589-018-0198-xThe bacteria that move…

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<i>N</i><sup>6-</sup>Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation

Posted on Dec 10th, 2018 - By Honghui Ma

N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation<i>N</i><sup>6-</sup>Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation, Published online: 10 December 2018; doi:10.1038/s41589-018-0184-3ZCCHC4 was identified as a mammalian ribosome RNA (rRNA) N6-methyladenosine (m6A) writer protein that installs m6A 4220 in 28S rRNA. 28S rRNA methylation affects global translation and cell growth and contributes to tumorigenesis in…

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Design of fast proteolysis-based signaling and logic circuits in mammalian cells

Posted on Dec 10th, 2018 - By Tina Fink

Design of fast proteolysis-based signaling and logic circuits in mammalian cellsDesign of fast proteolysis-based signaling and logic circuits in mammalian cells, Published online: 10 December 2018; doi:10.1038/s41589-018-0181-6Protease-cleavable orthogonal-coiled-coil-based (SPOC) systems, in which split viral proteases are activated by small molecules and cleave coiled-coil protease substrates, reprogram signaling with rapid kinetics in mammalian…

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Structures shed light on prostanoid signaling

Posted on Dec 3rd, 2018 - By Kaspar Hollenstein

Structures shed light on prostanoid signalingStructures shed light on prostanoid signaling, Published online: 03 December 2018; doi:10.1038/s41589-018-0178-1Prostanoids signal through G-protein-coupled receptors to regulate diverse physiological processes. Structures of three prostanoid receptors in inactive and active conformations now uncover the molecular determinants of ligand recognition and receptor activation and offer new opportunities for drug…

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Crystal structure of misoprostol bound to the labor inducer prostaglandin E<sub>2</sub> receptor

Posted on Dec 3rd, 2018 - By Martin Audet

Crystal structure of misoprostol bound to the labor inducer prostaglandin E2 receptorCrystal structure of misoprostol bound to the labor inducer prostaglandin E<sub>2</sub> receptor, Published online: 03 December 2018; doi:10.1038/s41589-018-0160-yA structure of the prostaglandin E2 receptor 3 (EP3) bound to the agonist misoprostol shows a completely enclosed binding pocket with a structured water molecule that coordinates misoprostol's ring structure and explains the receptor's…

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Programmable and printable <i>Bacillus subtilis</i> biofilms as engineered living materials

Posted on Dec 3rd, 2018 - By Jiaofang Huang

Programmable and printable Bacillus subtilis biofilms as engineered living materialsProgrammable and printable <i>Bacillus subtilis</i> biofilms as engineered living materials, Published online: 03 December 2018; doi:10.1038/s41589-018-0169-2Co-opting the amyloid machinery from Bacillus subtilis, engineering of TasA fusion proteins enables the assembly of functionalized biofilms with tunable physicochemical properties that are amenable to 3D printing and microencapsulation…

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Ligand binding to human prostaglandin E receptor EP<sub>4</sub> at the lipid-bilayer interface

Posted on Dec 3rd, 2018 - By Yosuke Toyoda

Ligand binding to human prostaglandin E receptor EP4 at the lipid-bilayer interfaceLigand binding to human prostaglandin E receptor EP<sub>4</sub> at the lipid-bilayer interface, Published online: 03 December 2018; doi:10.1038/s41589-018-0131-3The structure of human prostaglandin E receptor EP4 in complex with antagonist ONO-AE3-208 and a functional antibody reveals a ligand-binding site at the interface of the lipid bilayer that is unique among…

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Structural basis for ligand recognition of the human thromboxane A<sub>2</sub> receptor

Posted on Dec 3rd, 2018 - By Hengxin Fan

Structural basis for ligand recognition of the human thromboxane A2 receptorStructural basis for ligand recognition of the human thromboxane A<sub>2</sub> receptor, Published online: 03 December 2018; doi:10.1038/s41589-018-0170-9Structures of the human thromboxane A2 receptor, a member of the prostanoid family of G-protein-coupled receptors, in complex with two synthetic antagonists reveal that ligands access the ligand-binding pocket from the plane of the lipid…

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Crystal structure of the endogenous agonist-bound prostanoid receptor EP3

Posted on Dec 3rd, 2018 - By Kazushi Morimoto

Crystal structure of the endogenous agonist-bound prostanoid receptor EP3Crystal structure of the endogenous agonist-bound prostanoid receptor EP3, Published online: 03 December 2018; doi:10.1038/s41589-018-0171-8Structural analysis of prostaglandin E receptor EP3, a member of the prostanoid receptor subfamily of GPCRs, in complex with the endogenous agonist PGE2 reveals important interactions and motions required for receptor…

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Publisher Correction: Structural insights into binding specificity, efficacy and bias of a β<sub>2</sub>AR partial agonist

Posted on Nov 30th, 2018 - By Matthieu Masureel

Publisher Correction: Structural insights into binding specificity, efficacy and bias of a β2AR partial agonistPublisher Correction: Structural insights into binding specificity, efficacy and bias of a β<sub>2</sub>AR partial agonist, Published online: 30 November 2018; doi:10.1038/s41589-018-0182-5Publisher Correction: Structural insights into binding specificity, efficacy and bias of a β2AR partial…

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<i>Escherichia</i> coli “Marionette” strains with 12 highly optimized small-molecule sensors

Posted on Nov 26th, 2018 - By Adam J. Meyer

Escherichia coli “Marionette” strains with 12 highly optimized small-molecule sensors<i>Escherichia</i> coli “Marionette” strains with 12 highly optimized small-molecule sensors, Published online: 26 November 2018; doi:10.1038/s41589-018-0168-3A directed evolution approach was applied to optimize a set of 12 small-molecule-responsive biosensors, which led to the engineering of “Marionette” strains of Escherichia coli incorporating these sensors for biotechnological…

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Polarized displacement by transcription activator-like effectors for regulatory circuits

Posted on Nov 19th, 2018 - By Tina Lebar

Polarized displacement by transcription activator-like effectors for regulatory circuitsPolarized displacement by transcription activator-like effectors for regulatory circuits, Published online: 19 November 2018; doi:10.1038/s41589-018-0163-8The observation that transcription activator-like effectors (TALES) displace TALES bound at adjacent downstream DNA enables engineered regulation of gene expression, displacement of other DNA binding proteins and construction of logic-gated…

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Transcriptional recorder

Posted on Nov 14th, 2018 - By Yiyun Song

Transcriptional recorderTranscriptional recorder, Published online: 14 November 2018; doi:10.1038/s41589-018-0174-5Transcriptional…

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Expanding the terpenoid kingdom

Posted on Nov 14th, 2018 - By Yongjin J. Zhou

Expanding the terpenoid kingdomExpanding the terpenoid kingdom, Published online: 14 November 2018; doi:10.1038/s41589-018-0167-4Terpenoids are assembled from five-carbon (C5) units, which limits the available scaffold chemical space for the discovery of bioactive molecules. A combination of enzyme and metabolic engineering now enables biosynthesis of a plethora of non-natural C11…

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Disrupting the CD95–PLCγ1 interaction prevents Th17-driven inflammation

Posted on Nov 14th, 2018 - By Amanda Poissonnier

Disrupting the CD95–PLCγ1 interaction prevents Th17-driven inflammationDisrupting the CD95–PLCγ1 interaction prevents Th17-driven inflammation, Published online: 14 November 2018; doi:10.1038/s41589-018-0162-9The HIV protease inhibitor ritonavir targets the calcium-inducing domain (CID) of CD95 to block interactions with PLCγ1. Peptidomimetics targeting the CD95 CID prevents accumulation of inflammatory Th17 cells observed in systemic lupus…

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Synthesis of 11-carbon terpenoids in yeast using protein and metabolic engineering

Posted on Nov 14th, 2018 - By Codruta Ignea

Synthesis of 11-carbon terpenoids in yeast using protein and metabolic engineeringSynthesis of 11-carbon terpenoids in yeast using protein and metabolic engineering, Published online: 14 November 2018; doi:10.1038/s41589-018-0166-5Yeast engineered to produce the six-carbon terpene building block 2-methyl-geranyl diphosphate, coupled with terpene synthases engineered to accept this noncanonical substrate, enables the biosynthesis of a collection of new C11 terpenoid…

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Failure to convert

Posted on Nov 14th, 2018 - By Grant Miura

Failure to convertFailure to convert, Published online: 14 November 2018; doi:10.1038/s41589-018-0172-7Failure to…

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Identification of <i>Chaoborus</i> kairomone chemicals that induce defences in <i>Daphnia</i>

Posted on Nov 14th, 2018 - By Linda C. Weiss

Identification of Chaoborus kairomone chemicals that induce defences in DaphniaIdentification of <i>Chaoborus</i> kairomone chemicals that induce defences in <i>Daphnia</i>, Published online: 14 November 2018; doi:10.1038/s41589-018-0164-7The freshwater microcrustacean Daphnia pulex forms defensive neckteeth in response to a collection of chemical cues (the kairomone), now identified as certain fatty acids conjugated to glutamine, released during digestion by its…

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Metal Enterococcus equipment

Posted on Nov 14th, 2018 - By Mirella Bucci

Metal Enterococcus equipmentMetal Enterococcus equipment, Published online: 14 November 2018; doi:10.1038/s41589-018-0173-6Metal Enterococcus…

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Devilish diatoms

Posted on Nov 14th, 2018 - By Caitlin Deane

Devilish diatomsDevilish diatoms, Published online: 14 November 2018; doi:10.1038/s41589-018-0175-4Devilish…

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HIP1R targets PD-L1 to lysosomal degradation to alter T cell–mediated cytotoxicity

Posted on Nov 5th, 2018 - By Huanbin Wang

HIP1R targets PD-L1 to lysosomal degradation to alter T cell–mediated cytotoxicityHIP1R targets PD-L1 to lysosomal degradation to alter T cell–mediated cytotoxicity, Published online: 05 November 2018; doi:10.1038/s41589-018-0161-xHIP1R directly interacts with PD-L1 and targets PD-L1 for lysosomal degradation. Development of a rationally designed peptide incorporating the PD-L1 binding sequence of HIP1R with a lysosomal targeting sequence promotes PD-L1…

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The multicatalytic compartment of propionyl-CoA synthase sequesters a toxic metabolite

Posted on Oct 29th, 2018 - By Iria Bernhardsgrütter

The multicatalytic compartment of propionyl-CoA synthase sequesters a toxic metaboliteThe multicatalytic compartment of propionyl-CoA synthase sequesters a toxic metabolite, Published online: 29 October 2018; doi:10.1038/s41589-018-0153-xStructural and biochemical analysis of propionyl-CoA synthase reveals that it forms a reaction chamber containing three active sites, which sequesters the reactive intermediate acrylyl-CoA during the conversion of 3-hydroxypropionate to…

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Structure-guided development of YEATS domain inhibitors by targeting π-π-π stacking

Posted on Oct 29th, 2018 - By Xin Li

Structure-guided development of YEATS domain inhibitors by targeting π-π-π stackingStructure-guided development of YEATS domain inhibitors by targeting π-π-π stacking, Published online: 29 October 2018; doi:10.1038/s41589-018-0144-yAn inhibitor of the YEATS domain was developed by targeting a unique π-π-π stacking in the YEATS–Kcr recognition. An ENL YEATS-selective inhibitor, XL-13m, helps probe the YEATS-dependent role of ENL in the leukemogenic transcription…

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Identification of a cellularly active SIRT6 allosteric activator

Posted on Oct 29th, 2018 - By Zhimin Huang

Identification of a cellularly active SIRT6 allosteric activatorIdentification of a cellularly active SIRT6 allosteric activator, Published online: 29 October 2018; doi:10.1038/s41589-018-0150-0The use of an allosteric drug-design method resulted in the identification of a first-in-class cellularly active SIRT6 activator that induces cell-cycle arrest in the G0–G1 phase, thus suppressing proliferation in human hepatocellular carcinoma…

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Structural insights into binding specificity, efficacy and bias of a β<sub>2</sub>AR partial agonist

Posted on Oct 16th, 2018 - By Matthieu Masureel

Structural insights into binding specificity, efficacy and bias of a β2AR partial agonistStructural insights into binding specificity, efficacy and bias of a β<sub>2</sub>AR partial agonist, Published online: 16 October 2018; doi:10.1038/s41589-018-0145-xThe active-state structure of a GPCR occupied by a partial agonist, β2AR with salmeterol, together with mutagenesis and biophysical studies, explains this ligand's unusual pharmacological…

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A new spot for PKR

Posted on Oct 16th, 2018 - By Yiyun Song

A new spot for PKRA new spot for PKR, Published online: 16 October 2018; doi:10.1038/s41589-018-0159-4A new spot for…

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Metabolic repair through emergence of new pathways in <i>Escherichia coli</i>

Posted on Oct 16th, 2018 - By Sammy Pontrelli

Metabolic repair through emergence of new pathways in Escherichia coliMetabolic repair through emergence of new pathways in <i>Escherichia coli</i>, Published online: 16 October 2018; doi:10.1038/s41589-018-0149-6In response to the deletion of key genes involved in biosynthesis of the essential CoA precursor β-alanine, Escherichia coli overcomes this pathway damage by successively evolving alternative metabolic…

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Chaperoning partners

Posted on Oct 16th, 2018 - By Grant Miura

Chaperoning partnersChaperoning partners, Published online: 16 October 2018; doi:10.1038/s41589-018-0157-6Chaperoning…

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Enzyme promiscuity drives branched-chain fatty acid synthesis in adipose tissues

Posted on Oct 16th, 2018 - By Martina Wallace

Enzyme promiscuity drives branched-chain fatty acid synthesis in adipose tissuesEnzyme promiscuity drives branched-chain fatty acid synthesis in adipose tissues, Published online: 16 October 2018; doi:10.1038/s41589-018-0132-2mmBCFAs are endogenous fatty acids synthesized from BCAAs by brown and white adipose tissue via CrAT and FASN promiscuity. BCAA catabolism and mmBCFA lipogenesis are decreased by obesity-induced adipose hypoxia and influenced by the…

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No more ESKAPE

Posted on Oct 16th, 2018 - By Mirella Bucci

No more ESKAPENo more ESKAPE, Published online: 16 October 2018; doi:10.1038/s41589-018-0156-7No more…

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Small-molecule-based regulation of RNA-delivered circuits in mammalian cells

Posted on Oct 16th, 2018 - By Tyler E. Wagner

Small-molecule-based regulation of RNA-delivered circuits in mammalian cellsSmall-molecule-based regulation of RNA-delivered circuits in mammalian cells, Published online: 16 October 2018; doi:10.1038/s41589-018-0146-9Engineering of small-molecule-responsive RNA-binding proteins enables chemical regulation of modified mRNA or RNA replicon expression within mammalian cells for applications in synthetic circuit design and RNA-centered…

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Trading on thionoesters

Posted on Oct 16th, 2018 - By Caitlin Deane

Trading on thionoestersTrading on thionoesters, Published online: 16 October 2018; doi:10.1038/s41589-018-0158-5Trading on…

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Compartmentalizing acid stress in bacteria

Posted on Oct 15th, 2018 - By Colin Kleanthous

Compartmentalizing acid stress in bacteriaCompartmentalizing acid stress in bacteria, Published online: 15 October 2018; doi:10.1038/s41589-018-0148-7A Donnan equilibrium causes an influx of chloride ions into the Escherichia coli periplasm when the bacterium finds itself in gastric fluid. The combination of low pH and high anion concentration drives proteins to aggregate, a potentially lethal event unless prevented by specific…

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In vivo chloride concentrations surge to proteotoxic levels during acid stress

Posted on Oct 15th, 2018 - By Frederick Stull

In vivo chloride concentrations surge to proteotoxic levels during acid stressIn vivo chloride concentrations surge to proteotoxic levels during acid stress, Published online: 15 October 2018; doi:10.1038/s41589-018-0143-zProtonation of periplasmic protein carboxylic groups creates a Donnan equilibrium in the bacterial periplasmic space at low pH, leading to accumulation of Cl− and unfolding and aggregation of periplasmic proteins, which can be rescued by…

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The splice is right

Posted on Oct 15th, 2018 - By James Palacino

The splice is rightThe splice is right, Published online: 15 October 2018; doi:10.1038/s41589-018-0147-8Current drug discovery efforts focus on proteins because of their ability to form stable, structured pockets. A recent study demonstrates that targeting stable, structured bioactive RNA motifs, such as autocatalytic introns, may provide a novel method of expanding druggability and…

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Small molecules that target group II introns are potent antifungal agents

Posted on Oct 15th, 2018 - By Olga Fedorova

Small molecules that target group II introns are potent antifungal agentsSmall molecules that target group II introns are potent antifungal agents, Published online: 15 October 2018; doi:10.1038/s41589-018-0142-0High-throughput screening followed by an examination of structure–activity relationship-based optimization resulted in the identification of potent small-molecule inhibitors of group IIB intron splicing in fungal…

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New tricks for an old drug

Posted on Oct 8th, 2018 - By Barbara S. Nelson

New tricks for an old drugNew tricks for an old drug, Published online: 08 October 2018; doi:10.1038/s41589-018-0137-xThe prodrug dimethyloxalylglycine (DMOG) is a well-known tool compound used to study hypoxia. New findings reveal that DMOG also inhibits glutamine metabolism and can be exploited to selectively kill some cancer cells, highlighting important caveats when using DMOG for hypoxia…

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MCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOG

Posted on Oct 8th, 2018 - By Louise Fets

MCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOGMCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOG, Published online: 08 October 2018; doi:10.1038/s41589-018-0136-yHigh intracellular concentrations of the α-ketoglutarate analog N-oxalylglycine, owing to MCT2-mediated transport of its newly described prodrug MOG, inhibit multiple enzymes in glutamine metabolism and selectively kill MCT2-expressing cancer…

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Diversifying bases

Posted on Sep 17th, 2018 - By Yiyun Song

Diversifying basesDiversifying bases, Published online: 17 September 2018; doi:10.1038/s41589-018-0141-1Diversifying…

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A new target for thalidomide

Posted on Sep 17th, 2018 - By Peter G. Wells

A new target for thalidomideA new target for thalidomide, Published online: 17 September 2018; doi:10.1038/s41589-018-0134-0One mechanism of thalidomide teratogenicity involves binding to the CUL4–CRBN E3 ubiquitin ligase complex, which then mediates the degradation of transcription factors. New studies reveal that species-specific variants of the transcription factor SALL4 are differentially ubiquitinated and degraded via the thalidomide-bound…

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Cost–benefit analysis

Posted on Sep 17th, 2018 - By Grant Miura

Cost–benefit analysisCost–benefit analysis, Published online: 17 September 2018; doi:10.1038/s41589-018-0139-8Cost–benefit…

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T cell receptor cross-reactivity expanded by dramatic peptide–MHC adaptability

Posted on Sep 17th, 2018 - By Timothy P. Riley

T cell receptor cross-reactivity expanded by dramatic peptide–MHC adaptabilityT cell receptor cross-reactivity expanded by dramatic peptide–MHC adaptability, Published online: 17 September 2018; doi:10.1038/s41589-018-0130-4Structural analysis shows that cross-reactivity of the T cell receptor DMF5 is governed by adaptability of the peptide antigen, which can undergo TCR-binding-induced frameshifting forcing the peptide C terminus to extend from the MHC-binding…

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Post-translational site-selective protein backbone α-deuteration

Posted on Sep 17th, 2018 - By Sébastien R. G. Galan

Post-translational site-selective protein backbone α-deuterationPost-translational site-selective protein backbone α-deuteration, Published online: 17 September 2018; doi:10.1038/s41589-018-0128-yA chemical method for site-selective deuterium exchange at protein backbone α-carbons, involving conversion of cysteine to dehydroalanine and then to deuterated cysteine, is used to explore the mechanism of a model protein bioconjugation…

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The substrate lends a hand

Posted on Sep 17th, 2018 - By Albert A. Bowers

The substrate lends a hand The substrate lends a hand, Published online: 17 September 2018; doi:10.1038/s41589-018-0135-zDuramycin is a small post-translationally modified peptide with antibody-like affinity for phosphatidylethanolamine. As it turns out, the same functionality that is essential for duramycin activity helps to catalyze the formation of its conformationally constrained and compact polycyclic…

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Fatal chemoattraction

Posted on Sep 17th, 2018 - By Mirella Bucci

Fatal chemoattractionFatal chemoattraction, Published online: 17 September 2018; doi:10.1038/s41589-018-0140-2Fatal…

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Flipping out the peptide

Posted on Sep 17th, 2018 - By Stephanie Gras

Flipping out the peptideFlipping out the peptide, Published online: 17 September 2018; doi:10.1038/s41589-018-0133-1T cell cross-reactivity enables the immune system to recognize a large array of peptides. A new study shows that T cells can achieve cross-recognition by using the remarkable plasticity of peptides, through flipping the peptide out of the binding…

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SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate

Posted on Sep 6th, 2018 - By Mary E. Matyskiela

SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrateSALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate, Published online: 06 September 2018; doi:10.1038/s41589-018-0129-xThalidomide-induced degradation of the transcription factor SALL4 in a cereblon-dependent manner provides an explanation for the teratogenic…

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Establishment of the PAR-1 cortical gradient by the aPKC-PRBH circuit

Posted on Sep 3rd, 2018 - By Ravikrishna Ramanujam

Establishment of the PAR-1 cortical gradient by the aPKC-PRBH circuitEstablishment of the PAR-1 cortical gradient by the aPKC-PRBH circuit, Published online: 03 September 2018; doi:10.1038/s41589-018-0117-1The asymmetric cortical gradient of PAR-1 is patterned via an integration of its cortical exclusion and stabilization by a circuit consisting of aPKC and the PRBH protein…

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Substrate-assisted enzymatic formation of lysinoalanine in duramycin

Posted on Sep 3rd, 2018 - By Linna An

Substrate-assisted enzymatic formation of lysinoalanine in duramycinSubstrate-assisted enzymatic formation of lysinoalanine in duramycin, Published online: 03 September 2018; doi:10.1038/s41589-018-0122-4During the biosynthesis of the lanthipeptide duramycin, DurN catalyzes stereospecific lysinoalanine formation by preorganizing the reactive conformation of the substrate, such that one of the substrate’s own residues serves as the catalytic…

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Chemical proteomics reveals new targets of cysteine sulfinic acid reductase

Posted on Sep 3rd, 2018 - By Salma Akter

Chemical proteomics reveals new targets of cysteine sulfinic acid reductaseChemical proteomics reveals new targets of cysteine sulfinic acid reductase, Published online: 03 September 2018; doi:10.1038/s41589-018-0116-2An electrophilic diazene probe (DiaAlk) enables capture and proteomic analysis of cysteine S-sulfinylation modifications, thus illuminating dynamic responses to oxidative stress and enabling the identification of new substrates of…

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Nuclear RNR-α antagonizes cell proliferation by directly inhibiting ZRANB3

Posted on Aug 27th, 2018 - By Yuan Fu

Nuclear RNR-α antagonizes cell proliferation by directly inhibiting ZRANB3Nuclear RNR-α antagonizes cell proliferation by directly inhibiting ZRANB3, Published online: 27 August 2018; doi:10.1038/s41589-018-0113-5The large subunit of ribonucleotide reductase RNR-α downregulates DNA replication in the nucleus by directly disrupting PCNA and ZRANB3 interactions. RNR-α nuclear entry is regulated by an interplay between IRBIT and…

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Acetate-dependent tRNA acetylation required for decoding fidelity in protein synthesis

Posted on Aug 27th, 2018 - By Takaaki Taniguchi

Acetate-dependent tRNA acetylation required for decoding fidelity in protein synthesisAcetate-dependent tRNA acetylation required for decoding fidelity in protein synthesis, Published online: 27 August 2018; doi:10.1038/s41589-018-0119-zA comparative genomic approach identified a novel acetate-dependent tRNA-modifying enzyme that catalyzes RNA acetylation with a mechanism similar to tRNA aminoacylation. This modification maintains decoding fidelity in protein…

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<i>O</i>-GlcNAc modification of eIF4GI acts as a translational switch in heat shock response

Posted on Aug 20th, 2018 - By Xingqian Zhang

O-GlcNAc modification of eIF4GI acts as a translational switch in heat shock response<i>O</i>-GlcNAc modification of eIF4GI acts as a translational switch in heat shock response, Published online: 20 August 2018; doi:10.1038/s41589-018-0120-6O-GlcNAcylation of translation initiation factor component eIF4GI blocks interactions to poly(A)-binding protein Pab1 to induce disassembly of stress granules, releasing Hsp70-induced mRNAs and leading to translation of protective…

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Continuous directed evolution of proteins with improved soluble expression

Posted on Aug 20th, 2018 - By Tina Wang

Continuous directed evolution of proteins with improved soluble expressionContinuous directed evolution of proteins with improved soluble expression, Published online: 20 August 2018; doi:10.1038/s41589-018-0121-5Through use of a split-intein pIII, soluble expression phage-assisted continuous evolution (SE-PACE) enables two simultaneous positive selections to rapidly evolve proteins with improved expression while maintaining their desired…

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<i>ykkC</i> riboswitches employ an add-on helix to adjust specificity for polyanionic ligands

Posted on Aug 17th, 2018 - By Alla Peselis

ykkC riboswitches employ an add-on helix to adjust specificity for polyanionic ligands<i>ykkC</i> riboswitches employ an add-on helix to adjust specificity for polyanionic ligands, Published online: 17 August 2018; doi:10.1038/s41589-018-0114-4Structural analysis of PRPP and ppGpp riboswitches reveals that they employ a helical element to create a tunnel for the ligand, whose specificity is determined by the conserved nucleotides forming the tunnel and long-distance…

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TA gets a PG rating

Posted on Aug 17th, 2018 - By Mirella Bucci

TA gets a PG ratingTA gets a PG rating, Published online: 17 August 2018; doi:10.1038/s41589-018-0126-0TA gets a PG…

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Stuck on you

Posted on Aug 17th, 2018 - By Caitlin Deane

Stuck on youStuck on you, Published online: 17 August 2018; doi:10.1038/s41589-018-0124-2Stuck on…

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Mimicking cross-α amyloids

Posted on Aug 17th, 2018 - By Meytal Landau

Mimicking cross-α amyloidsMimicking cross-α amyloids, Published online: 17 August 2018; doi:10.1038/s41589-018-0118-0The design of spiraling cross-α amyloid-like structures reveals fascinating supermolecular fibrils of diverse compactness and stability. The small sequence variations governing cross-α self-assembly properties concur with amyloids being basic building blocks of life and natural targets for microbial structural…

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Allosteric mechanisms underlie GPCR signaling to SH3-domain proteins through arrestin

Posted on Aug 17th, 2018 - By Fan Yang

Allosteric mechanisms underlie GPCR signaling to SH3-domain proteins through arrestinAllosteric mechanisms underlie GPCR signaling to SH3-domain proteins through arrestin, Published online: 17 August 2018; doi:10.1038/s41589-018-0115-3NMR and in vitro reconstitution indicate that GPCRs signal through SH3-containing proteins downstream of β-arrestin 1 proline regions and that arrestin allosterically activates downstream kinases by disrupting their autoinhibitory…

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An optical sensor to monitor dynamics of extracellular glycine

Posted on Aug 17th, 2018 - By Dmitri A. Rusakov

An optical sensor to monitor dynamics of extracellular glycineAn optical sensor to monitor dynamics of extracellular glycine, Published online: 17 August 2018; doi:10.1038/s41589-018-0123-3A computational design approach was used to develop a genetically encoded FRET-based optical sensor that is aimed at monitoring extracellular glycine levels in brain tissue with the sensitivity and resolution to discern differences in dendritic spine and shaft environment and concentration dynamics upon…

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Catch and identify your prey

Posted on Aug 17th, 2018 - By Karin Kuehnel

Catch and identify your preyCatch and identify your prey, Published online: 17 August 2018; doi:10.1038/s41589-018-0125-1Catch and identify your…

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A ribonucleotide trap

Posted on Aug 17th, 2018 - By Yiyun Song

A ribonucleotide trapA ribonucleotide trap, Published online: 17 August 2018; doi:10.1038/s41589-018-0127-zA ribonucleotide…

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Designed peptides that assemble into cross-α amyloid-like structures

Posted on Jul 30th, 2018 - By Shao-Qing Zhang

Designed peptides that assemble into cross-α amyloid-like structuresDesigned peptides that assemble into cross-α amyloid-like structures, Published online: 30 July 2018; doi:10.1038/s41589-018-0105-5Structural analysis reveals how certain designed peptides adopt unusual spiraling cross-α amyloid-like structures and also rearrange to helical polymers upon mutation of small nonpolar residues that are critical for packing and…

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Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS

Posted on Jul 30th, 2018 - By William H. Zhang

Monitoring hippocampal glycine with the computationally designed optical sensor GlyFSMonitoring hippocampal glycine with the computationally designed optical sensor GlyFS, Published online: 30 July 2018; doi:10.1038/s41589-018-0108-2A genetically encoded FRET-based optical sensor generated from a computational design approach can monitor hippocampal glycine levels in brain tissue to determine differences between spines and shafts and changes induced by high- and low-frequency…

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A multicolor riboswitch-based platform for imaging of RNA in live mammalian cells

Posted on Jul 30th, 2018 - By Esther Braselmann

A multicolor riboswitch-based platform for imaging of RNA in live mammalian cellsA multicolor riboswitch-based platform for imaging of RNA in live mammalian cells, Published online: 30 July 2018; doi:10.1038/s41589-018-0103-7A new riboswitch-based RNA sensor called Riboglow binds to quenched fluorescent probes to induce fluorescence turn-on. Riboglow enables tagging and tracking of mRNA and short noncoding RNAs with different colored fluorophores in live mammalian…

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Gramibactin is a bacterial siderophore with a diazeniumdiolate ligand system

Posted on Jul 30th, 2018 - By Ron Hermenau

Gramibactin is a bacterial siderophore with a diazeniumdiolate ligand systemGramibactin is a bacterial siderophore with a diazeniumdiolate ligand system, Published online: 30 July 2018; doi:10.1038/s41589-018-0101-9Plant-associated rhizosphere bacteria produce gramibactin, a cyclic lipodepsipeptide siderophore that tightly binds iron via an unexpected functional group, the N-nitrosohydroxylamine (diazeniumdiolate) moieties of the amino acid…

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3D interaction hubs

Posted on Jul 17th, 2018 - By Yiyun Song

3D interaction hubs3D interaction hubs, Published online: 17 July 2018; doi:10.1038/s41589-018-0112-63D interaction…

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Antigen processing movers and shakers

Posted on Jul 17th, 2018 - By Tim Elliott

Antigen processing movers and shakersAntigen processing movers and shakers, Published online: 17 July 2018; doi:10.1038/s41589-018-0106-4Monitoring MHC-I dynamics upon binding to its chaperone TAPBPR helps us understand how optimal peptide sequences are selected for presentation and coordinated with release of the chaperone from the ternary peptide–MHC-I–TAPBPR…

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Caught in the act

Posted on Jul 17th, 2018 - By Karin Kuehnel

Caught in the actCaught in the act, Published online: 17 July 2018; doi:10.1038/s41589-018-0110-8Caught in the…

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Dopamine gets lit

Posted on Jul 17th, 2018 - By Mirella Bucci

Dopamine gets litDopamine gets lit, Published online: 17 July 2018; doi:10.1038/s41589-018-0111-7Dopamine gets…

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A remote control for switching

Posted on Jul 17th, 2018 - By Marc Vendrell

A remote control for switchingA remote control for switching, Published online: 17 July 2018; doi:10.1038/s41589-018-0107-3Calcium channels are crucial regulators of a broad range of biological processes. A photoswitchable chemical probe allows the opening and closing of these channels with unprecedented temporal resolution, providing new opportunities to study calcium-dependent signaling pathways in real…

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Crowd control

Posted on Jul 17th, 2018 - By Grant Miura

Crowd controlCrowd control, Published online: 17 July 2018; doi:10.1038/s41589-018-0109-1Crowd…

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Facile target validation in an animal model with intracellularly expressed monobodies

Posted on Jul 16th, 2018 - By Ankit Gupta

Facile target validation in an animal model with intracellularly expressed monobodiesFacile target validation in an animal model with intracellularly expressed monobodies, Published online: 16 July 2018; doi:10.1038/s41589-018-0099-zThe development of a selective and potent monobody to WDR5, a component of the mixed linear leukemia methyltransferase complex, as genetically encoded inhibitor enables suppression of leukemogenesis and confers survival in a mouse leukemia…

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Acetylation blocks DNA damage–induced chromatin ADP-ribosylation

Posted on Jul 16th, 2018 - By Glen Liszczak

Acetylation blocks DNA damage–induced chromatin ADP-ribosylationAcetylation blocks DNA damage–induced chromatin ADP-ribosylation, Published online: 16 July 2018; doi:10.1038/s41589-018-0097-1Histone H3 serine 10 is found to be the major chromatin acceptor residue for DNA damage–induced ADP-ribosylation and is blocked by specific acetylation sites on PARP1 and/or…

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PAINTing translation

Posted on Jul 9th, 2018 - By Yuichiro Mishima

PAINTing translationPAINTing translation, Published online: 09 July 2018; doi:10.1038/s41589-018-0102-8Establishment of the germ cell lineage requires post-transcriptional regulation of mRNAs, yet the underlying molecular mechanisms are not fully understood in vertebrates. A small-molecule inhibitor of germ cell formation reveals a noncanonical translation system used in zebrafish…

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Noncanonical translation via deadenylated 3′ UTRs maintains primordial germ cells

Posted on Jul 9th, 2018 - By Youngnam N. Jin

Noncanonical translation via deadenylated 3′ UTRs maintains primordial germ cellsNoncanonical translation via deadenylated 3′ UTRs maintains primordial germ cells, Published online: 09 July 2018; doi:10.1038/s41589-018-0098-0Primordazine inhibits poly(A)-tail-independent noncanonical translation (PAINT) in early zebrafish embryos and in mammalian cells under select conditions, an effect mediated by deadenylated 3ʹ UTRs that results in ablation of primordial germ…

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Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle

Posted on Jul 9th, 2018 - By Andrew C. McShan

Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cyclePeptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle, Published online: 09 July 2018; doi:10.1038/s41589-018-0096-2Use of NMR to monitor MHC-I dynamics upon binding to the MHC-I chaperone TAPBPR explains the selection of optimal peptide sequences and release of the chaperone from the ternary peptide-MHC-I–TAPBPR…

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Publisher Correction: The Jumonji-C oxygenase JMJD7 catalyzes (3<i>S</i>)-lysyl hydroxylation of TRAFAC GTPases

Posted on Jun 27th, 2018 - By Suzana Markolovic

Publisher Correction: The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPasesPublisher Correction: The Jumonji-C oxygenase JMJD7 catalyzes (3<i>S</i>)-lysyl hydroxylation of TRAFAC GTPases, Published online: 27 June 2018; doi:10.1038/s41589-018-0104-6Publisher Correction: The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC…

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Metabolic engineering of a carbapenem antibiotic synthesis pathway in <i>Escherichia coli</i>

Posted on Jun 25th, 2018 - By Helena Shomar

Metabolic engineering of a carbapenem antibiotic synthesis pathway in Escherichia coliMetabolic engineering of a carbapenem antibiotic synthesis pathway in <i>Escherichia coli</i>, Published online: 25 June 2018; doi:10.1038/s41589-018-0084-6Efficient production of a simple carbapenem antibiotic in Escherichia coli is achieved by a combination of feedback-resistant enzymes for increased precursor biosynthesis and inhibition of fatty acid synthesis for tolerance toward the toxic…

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Cleavage of a carbon–fluorine bond by an engineered cysteine dioxygenase

Posted on Jun 25th, 2018 - By Jiasong Li

Cleavage of a carbon–fluorine bond by an engineered cysteine dioxygenaseCleavage of a carbon–fluorine bond by an engineered cysteine dioxygenase, Published online: 25 June 2018; doi:10.1038/s41589-018-0085-5Engineered variants of cysteine dioxygenase containing a halogen-substituted tyrosine analog provide insights into the process of Cys–Tyr cross-link formation and indicate that the enzyme can catalyze oxidative cleavage of a carbon–fluorine…

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Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer

Posted on Jun 25th, 2018 - By Hayley J. Donnella

Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancerKinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer, Published online: 25 June 2018; doi:10.1038/s41589-018-0081-9Proteomic mapping of dynamic changes in kinase signaling after drug treatment identifies that AURKA inhibition is required for drug sensitivity, representing a new co-targeting opportunity with PI3K, AKT, or mTOR inhibitors in breast…

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Unraveling the rewired network

Posted on Jun 25th, 2018 - By Vinayak Palve

Unraveling the rewired networkUnraveling the rewired network, Published online: 25 June 2018; doi:10.1038/s41589-018-0083-7Adaptive survival signaling can promote resistance to individual kinase inhibitors. A new study used a pathway-based approach to characterize shared kinome-wide rewiring mechanisms across multiple kinase inhibitors and developed rational drug-combination approaches that target cross-talk between two signaling…

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Designing microbial consortia with defined social interactions

Posted on Jun 25th, 2018 - By Wentao Kong

Designing microbial consortia with defined social interactionsDesigning microbial consortia with defined social interactions, Published online: 25 June 2018; doi:10.1038/s41589-018-0091-7Synthetic microbial consortia were engineered as experimental models of bacterial interactions within ecosystems, and mathematical models of their behavior were used to design more complex microbial systems with additional…

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Sarpagan bridge enzyme has substrate-controlled cyclization and aromatization modes

Posted on Jun 25th, 2018 - By Thu-Thuy T. Dang

Sarpagan bridge enzyme has substrate-controlled cyclization and aromatization modesSarpagan bridge enzyme has substrate-controlled cyclization and aromatization modes, Published online: 25 June 2018; doi:10.1038/s41589-018-0078-4Three homologous cytochrome P450s from monoterpene indole alkaloid-producing plants enable the identification of sarpagan bridge enzyme, which catalyzes either cyclization or aromatization to yield sarpagan or β-carboline alkaloids,…

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Single-molecule probing of the conformational homogeneity of the ABC transporter BtuCD

Posted on Jun 18th, 2018 - By Min Yang

Single-molecule probing of the conformational homogeneity of the ABC transporter BtuCDSingle-molecule probing of the conformational homogeneity of the ABC transporter BtuCD, Published online: 18 June 2018; doi:10.1038/s41589-018-0088-2A single-molecule approach combined with molecular dynamics simulations to examine the conformational dynamics of the Escherichia coli ABC transporter BtuCD defines a coordinated sequence of events leading to unidirectional…

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Scavenging of superoxide by a membrane-bound superoxide oxidase

Posted on Jun 18th, 2018 - By Camilla A. K. Lundgren

Scavenging of superoxide by a membrane-bound superoxide oxidaseScavenging of superoxide by a membrane-bound superoxide oxidase, Published online: 18 June 2018; doi:10.1038/s41589-018-0072-xThe membrane-bound enzyme CybB can directly oxidize superoxide to molecular oxygen and transfer the sequestered electrons to ubiquinone in vitro, providing a mechanism for superoxide scavenging distinct from that of superoxide…

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The anti-staphylococcal lipolanthines are ribosomally synthesized lipopeptides

Posted on Jun 18th, 2018 - By Vincent Wiebach

The anti-staphylococcal lipolanthines are ribosomally synthesized lipopeptidesThe anti-staphylococcal lipolanthines are ribosomally synthesized lipopeptides, Published online: 18 June 2018; doi:10.1038/s41589-018-0068-6The antibacterial microvionin contains two new lanthipeptide modifications, a triamino-dicarboxylic acid (avionin) and an N-terminal guanidino fatty acid, that lead to the establishment of the lipolanthine natural product…

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The Jumonji-C oxygenase JMJD7 catalyzes (3<i>S</i>)-lysyl hydroxylation of TRAFAC GTPases

Posted on Jun 18th, 2018 - By Suzana Markolovic

The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPasesThe Jumonji-C oxygenase JMJD7 catalyzes (3<i>S</i>)-lysyl hydroxylation of TRAFAC GTPases, Published online: 18 June 2018; doi:10.1038/s41589-018-0071-yStructural, biochemical and cellular studies reveal JMJD7 to be a Jumonji-C oxygenase that catalyzes (3S)-lysyl hydroxylation of the translation factor family of GTPases, DRG1 and…

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Vitamin B<sub>12</sub> import is all about timing

Posted on Jun 18th, 2018 - By Lutz Schmitt

Vitamin B12 import is all about timingVitamin B<sub>12</sub> import is all about timing, Published online: 18 June 2018; doi:10.1038/s41589-018-0087-3Single-molecule techniques combined with molecular dynamics simulations allowed visualization of a surprisingly high level of conformational homogeneity in the transport cycle of an ABC import system, BtuCD-F, and revealed an unexpected tight coupling of distinct conformational states responsible for vitamin B12 binding, transport and…

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Please hold for chaperones

Posted on Jun 18th, 2018 - By Caitlin Deane

Please hold for chaperonesPlease hold for chaperones, Published online: 18 June 2018; doi:10.1038/s41589-018-0092-6Please hold for…

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Tricks for taking up residence

Posted on Jun 18th, 2018 - By Mirella Bucci

Tricks for taking up residenceTricks for taking up residence, Published online: 18 June 2018; doi:10.1038/s41589-018-0094-4Tricks for taking up…

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Stabilizing synapsis

Posted on Jun 18th, 2018 - By Yiyun Song

Stabilizing synapsisStabilizing synapsis, Published online: 18 June 2018; doi:10.1038/s41589-018-0095-3Stabilizing…

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Linkers for protein degradation

Posted on Jun 11th, 2018 - By Philip P. Chamberlain

Linkers for protein degradationLinkers for protein degradation, Published online: 11 June 2018; doi:10.1038/s41589-018-0057-9The ability to subvert E3 ubiquitin ligases with small-molecule drugs offers tremendous promise for drug discovery. A new study demonstrates how structural and computational techniques can engineer and exploit unnatural protein–protein interfaces to design selective protein…

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Structural and genomic decoding of human and plant myristoylomes reveals a definitive recognition pattern

Posted on Jun 11th, 2018 - By Benoit Castrec

Structural and genomic decoding of human and plant myristoylomes reveals a definitive recognition patternStructural and genomic decoding of human and plant myristoylomes reveals a definitive recognition pattern, Published online: 11 June 2018; doi:10.1038/s41589-018-0077-5Aided by the solving of the structures of human NMT1 with substrate-mimicking peptides, mapping of human and Arabidopsis myristoylomes defines a myristoylation recognition motif and over 1,000 myristoylated protein…

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Plasticity in binding confers selectivity in ligand-induced protein degradation

Posted on Jun 11th, 2018 - By Radosław P. Nowak

Plasticity in binding confers selectivity in ligand-induced protein degradationPlasticity in binding confers selectivity in ligand-induced protein degradation, Published online: 11 June 2018; doi:10.1038/s41589-018-0055-ySelectivity of ligand-induced protein degradation and dimerization is conferred by plastic interprotein contacts. Computational protein–protein docking reveals the underlying interprotein contacts to inform the design of a BRD4 selective…

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