Fueled by light

Posted on Apr 16th, 2018 - By Grant Miura

Fueled by lightFueled by light, Published online: 16 April 2018; doi:10.1038/s41589-018-0048-xFueled by…

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The peptide <span class=”small-caps”>d</span>-list

Posted on Apr 16th, 2018 - By Mirella Bucci

The peptide d-listThe peptide <span class="small-caps">d</span>-list, Published online: 16 April 2018; doi:10.1038/s41589-018-0049-9The peptide…

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Structure in sequence

Posted on Apr 16th, 2018 - By Yiyun Song

Structure in sequenceStructure in sequence, Published online: 16 April 2018; doi:10.1038/s41589-018-0050-3Structure in…

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Dynamic coupling between conformations and nucleotide states in DNA gyrase

Posted on Apr 16th, 2018 - By Aakash Basu

Dynamic coupling between conformations and nucleotide states in DNA gyraseDynamic coupling between conformations and nucleotide states in DNA gyrase, Published online: 16 April 2018; doi:10.1038/s41589-018-0037-0Single-molecule measurements of DNA gyrase activity reveal conformational dynamics coupling ATP consumption to DNA…

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Designing macrocyclic disulfide-rich peptides for biotechnological applications

Posted on Apr 16th, 2018 - By Conan K. Wang

Designing macrocyclic disulfide-rich peptides for biotechnological applicationsDesigning macrocyclic disulfide-rich peptides for biotechnological applications, Published online: 16 April 2018; doi:10.1038/s41589-018-0039-yThrough molecular grafting, cyclic disulfide-rich peptides can be used as scaffolds to improve the stability, rigidity, and cellular uptake of bioactive peptides, although a number of factors should be considered when designing such grafted…

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Understanding the Pro/N-end rule pathway

Posted on Apr 16th, 2018 - By David A. Dougan

Understanding the Pro/N-end rule pathwayUnderstanding the Pro/N-end rule pathway, Published online: 16 April 2018; doi:10.1038/s41589-018-0045-0Regulated destruction of proteins underlies just about everything a cell does. A structural study of human Gid4, the N-recognin of the Pro/N-end rule pathway that targets proteins through their N-terminal proline, illuminates the recognition of substrates by this proteolytic…

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Spotting the signal

Posted on Apr 16th, 2018 - By Caitlin Deane

Spotting the signalSpotting the signal, Published online: 16 April 2018; doi:10.1038/s41589-018-0047-ySpotting the…

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Genome-wide mutant profiling predicts the mechanism of a Lipid II binding antibiotic

Posted on Apr 16th, 2018 - By Marina Santiago

Genome-wide mutant profiling predicts the mechanism of a Lipid II binding antibioticGenome-wide mutant profiling predicts the mechanism of a Lipid II binding antibiotic, Published online: 16 April 2018; doi:10.1038/s41589-018-0041-4Use of a combined Tn-seq and machine-learning approach for predicting mechanisms and targets of antibiotic action in Staphylococcus aureus shows that the natural product lysocin E (LysE) binds Lipid II on the cell surface and damages the…

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FINO<sub>2</sub> initiates ferroptosis through GPX4 inactivation and iron oxidation

Posted on Apr 2nd, 2018 - By Michael M. Gaschler

FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidationFINO<sub>2</sub> initiates ferroptosis through GPX4 inactivation and iron oxidation, Published online: 02 April 2018; doi:10.1038/s41589-018-0031-6FINO2 is a small molecule that requires the endoperoxide moiety and hydroxyl group to promote ferroptosis through indirect inhibition of GPX4 enzymatic function and direct oxidation of iron, resulting in increased lipid…

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Super-long single-molecule tracking reveals dynamic-anchorage-induced integrin function

Posted on Apr 2nd, 2018 - By Taka A. Tsunoyama

Super-long single-molecule tracking reveals dynamic-anchorage-induced integrin functionSuper-long single-molecule tracking reveals dynamic-anchorage-induced integrin function, Published online: 02 April 2018; doi:10.1038/s41589-018-0032-5Dissolved oxygen and a reducing-plus-oxidizing system suppress photobleaching and photoblinking in single-molecule tracking experiments, allowing long recordings of CD47 and integrin that showed temporary immobilization within focal…

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The structural organization of substrate loading in iterative polyketide synthases

Posted on Apr 2nd, 2018 - By Dominik A. Herbst

The structural organization of substrate loading in iterative polyketide synthasesThe structural organization of substrate loading in iterative polyketide synthases, Published online: 02 April 2018; doi:10.1038/s41589-018-0026-3The crystal structure and cryo-electron microscopy of the loading/condensing region of a nonreducing polyketide synthase reveals the insertion of a starter-unit acyltransferase into the condensing region and an asymmetrical post-loading…

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Author Correction: Mitochondrial DNA repair and replication proteins revealed by targeted chemical probes

Posted on Apr 2nd, 2018 - By Simon Wisnovsky

Author Correction: Mitochondrial DNA repair and replication proteins revealed by targeted chemical probesAuthor Correction: Mitochondrial DNA repair and replication proteins revealed by targeted chemical probes, Published online: 02 April 2018; doi:10.1038/s41589-018-0040-5Author Correction: Mitochondrial DNA repair and replication proteins revealed by targeted chemical…

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Unfolding of a ClC chloride transporter retains memory of its evolutionary history

Posted on Mar 26th, 2018 - By Duyoung Min

Unfolding of a ClC chloride transporter retains memory of its evolutionary historyUnfolding of a ClC chloride transporter retains memory of its evolutionary history, Published online: 26 March 2018; doi:10.1038/s41589-018-0025-4A single-molecule forced unfolding of E. coli chloride transporter ClC-ec1 shows that the N- and C-terminal halves of the protein unfold independently, with exposed polar surfaces stabilized by membrane lipid head groups and…

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Biosynthesis of redox-active metabolites in response to iron deficiency in plants

Posted on Mar 26th, 2018 - By Jakub Rajniak

Biosynthesis of redox-active metabolites in response to iron deficiency in plantsBiosynthesis of redox-active metabolites in response to iron deficiency in plants, Published online: 26 March 2018; doi:10.1038/s41589-018-0019-2The biosynthesis and secretion of redox-active coumarins sideretin and fraxetin in Arabidopsis thaliana enables the plant to acquire iron under nutrient-limited conditions and provides a blueprint for the use of related compounds in other…

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The dTAG system for immediate and target-specific protein degradation

Posted on Mar 26th, 2018 - By Behnam Nabet

The dTAG system for immediate and target-specific protein degradationThe dTAG system for immediate and target-specific protein degradation, Published online: 26 March 2018; doi:10.1038/s41589-018-0021-8The dTAG system pairs potent heterobifunctional degraders and extensible tagging strategies to achieve immediate and reversible degradation of divergent proteins, facilitating biological investigation and drug target validation in cells and in…

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TAGing for destruction

Posted on Mar 26th, 2018 - By Aisha Yesbolatova

TAGing for destructionTAGing for destruction, Published online: 26 March 2018; doi:10.1038/s41589-018-0024-5Proteins brought to an E3 ubiquitin ligase are polyubiquitylated for rapid degradation via the proteasome. A new study developed a tag-based degradation system using heterobifunctional degradation inducers called dTAGs, which rapidly depleted FKBP12F36V-fused proteins in cultured cells and in…

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Discovery of enzymes for toluene synthesis from anoxic microbial communities

Posted on Mar 19th, 2018 - By Harry R. Beller

Discovery of enzymes for toluene synthesis from anoxic microbial communitiesDiscovery of enzymes for toluene synthesis from anoxic microbial communities, Published online: 19 March 2018; doi:10.1038/s41589-018-0017-4The source of biological toluene production in diverse anoxic microbial communities is a glycyl radical enzyme that catalyzes phenylacetate decarboxylation (PhdB), and its cognate activating radical S-adenosylmethionine enzyme…

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A ‘cis’ted localization

Posted on Mar 19th, 2018 - By Mirella Bucci

A ‘cis’ted localizationA ‘cis’ted localization, Published online: 19 March 2018; doi:10.1038/s41589-018-0029-0A ‘cis’ted…

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RaPID hookup

Posted on Mar 19th, 2018 - By Grant Miura

RaPID hookupRaPID hookup, Published online: 19 March 2018; doi:10.1038/s41589-018-0030-7RaPID…

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An optically controlled probe identifies lipid-gating fenestrations within the TRPC3 channel

Posted on Mar 19th, 2018 - By Michaela Lichtenegger

An optically controlled probe identifies lipid-gating fenestrations within the TRPC3 channelAn optically controlled probe identifies lipid-gating fenestrations within the TRPC3 channel, Published online: 19 March 2018; doi:10.1038/s41589-018-0015-6A photoswitchable diacylglycerol enabled a screen that found critical TRPC3 lipid-sensing residues and identified a lateral fenestration in the pore domain that allows lipids to protrude into the permeation pathway to control channel…

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Specialized splicing

Posted on Mar 19th, 2018 - By Caitlin Deane

Specialized splicingSpecialized splicing, Published online: 19 March 2018; doi:10.1038/s41589-018-0027-2Specialized…

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Whole-organism phenotypic screening for anti-infectives promoting host health

Posted on Mar 19th, 2018 - By Anne E. Clatworthy

Whole-organism phenotypic screening for anti-infectives promoting host healthWhole-organism phenotypic screening for anti-infectives promoting host health, Published online: 19 March 2018; doi:10.1038/s41589-018-0018-3Targeting the host during antibiotic discovery efforts is a viable strategy, and the approach has benefited from phenotypic screening of model organisms such as worms, zebrafish, and…

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Structural basis for backbone N-methylation by an interrupted adenylation domain

Posted on Mar 19th, 2018 - By Shogo Mori

Structural basis for backbone N-methylation by an interrupted adenylation domainStructural basis for backbone N-methylation by an interrupted adenylation domain, Published online: 19 March 2018; doi:10.1038/s41589-018-0014-7The crystal structure of a methyltransferase domain embedded within an interrupted adenylation domain provides insight into how a nonribosomal peptide synthetase N-methylates amino acid precursors for their incorporation into the peptide…

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Mix and match

Posted on Mar 19th, 2018 - By Karin Kuehnel

Mix and matchMix and match, Published online: 19 March 2018; doi:10.1038/s41589-018-0028-1Mix and…

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Structural basis of the Cope rearrangement and cyclization in hapalindole biogenesis

Posted on Mar 12th, 2018 - By Sean A. Newmister

Structural basis of the Cope rearrangement and cyclization in hapalindole biogenesisStructural basis of the Cope rearrangement and cyclization in hapalindole biogenesis, Published online: 12 March 2018; doi:10.1038/s41589-018-0003-xThe structure of a Stig cyclase, HpiC1, reveals how it catalyzes Cope rearrangement and 6-exo-trig cyclization, including how it controls the position of electrophilic aromatic substation that distinguishes hapalindole from fischerindole…

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Publisher Correction: Oxidative demethylation of algal carbohydrates by cytochrome P450 monooxygenases

Posted on Mar 8th, 2018 - By Lukas Reisky

Publisher Correction: Oxidative demethylation of algal carbohydrates by cytochrome P450 monooxygenasesPublisher Correction: Oxidative demethylation of algal carbohydrates by cytochrome P450 monooxygenases, Published online: 08 March 2018; doi:10.1038/s41589-018-0020-9Publisher Correction: Oxidative demethylation of algal carbohydrates by cytochrome P450…

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Publisher Correction: A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters

Posted on Mar 8th, 2018 - By Kiryl D. Piatkevich

Publisher Correction: A robotic multidimensional directed evolution approach applied to fluorescent voltage reportersPublisher Correction: A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters, Published online: 08 March 2018; doi:10.1038/s41589-018-0023-6Publisher Correction: A robotic multidimensional directed evolution approach applied to fluorescent voltage…

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Publisher Correction: Resistance to nonribosomal peptide antibiotics mediated by <span class=”small-caps”>d</span>-stereospecific peptidases

Posted on Mar 7th, 2018 - By Yong-Xin Li

Publisher Correction: Resistance to nonribosomal peptide antibiotics mediated by d-stereospecific peptidasesPublisher Correction: Resistance to nonribosomal peptide antibiotics mediated by <span class="small-caps">d</span>-stereospecific peptidases, Published online: 07 March 2018; doi:10.1038/s41589-018-0022-7Publisher Correction: Resistance to nonribosomal peptide antibiotics mediated by d-stereospecific…

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Chaperones convert the energy from ATP into the nonequilibrium stabilization of native proteins

Posted on Mar 5th, 2018 - By Pierre Goloubinoff

Chaperones convert the energy from ATP into the nonequilibrium stabilization of native proteinsChaperones convert the energy from ATP into the nonequilibrium stabilization of native proteins, Published online: 05 March 2018; doi:10.1038/s41589-018-0013-8A nonequilibrium thermodynamic model can explain how molecular chaperones such as GroEL can use the energy from ATP hydrolysis to maintain substrate proteins in an active state, even under conditions that favor the substrate’s inactive…

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Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands

Posted on Mar 5th, 2018 - By Lara N. Gechijian

Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligandsFunctional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands, Published online: 05 March 2018; doi:10.1038/s41589-018-0010-ySelective TRIM24 degradation is achieved by co-opting the VHL E3 ubiquitin ligase machinery. TRIM24 degradation outperforms bromodomain inhibition, with an enhanced antiproliferative effect in acute leukemia, a novel context of TRIM24…

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A lanthipeptide library used to identify a protein–protein interaction inhibitor

Posted on Mar 5th, 2018 - By Xiao Yang

A lanthipeptide library used to identify a protein–protein interaction inhibitorA lanthipeptide library used to identify a protein–protein interaction inhibitor, Published online: 05 March 2018; doi:10.1038/s41589-018-0008-5The substrate-tolerant lanthipeptide synthetase ProcM enables the construction of a plasmid-encoded library of bicyclic lanthipeptides, from which an inhibitor of the p6–UEV protein–protein interaction is identified by a reverse two-hybrid…

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Regulation of apoptosis by an intrinsically disordered region of Bcl-xL

Posted on Mar 5th, 2018 - By Ariele Viacava Follis

Regulation of apoptosis by an intrinsically disordered region of Bcl-xLRegulation of apoptosis by an intrinsically disordered region of Bcl-xL, Published online: 05 March 2018; doi:10.1038/s41589-018-0011-xPost-translational modification of residues in an intrinsically disordered region of Bcl-XL promotes interactions with its folded core and allosterically reduces affinity for proapoptotic BH3-domain-containing proteins, resulting in…

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Folding against the wind

Posted on Mar 5th, 2018 - By Frederick Stull

Folding against the windFolding against the wind, Published online: 05 March 2018; doi:10.1038/s41589-018-0016-5Many thermodynamically unfavorable processes in biology are powered by ATP, the energy currency of the cell. New evidence suggests that chaperone-mediated protein stabilization may need to be added to that…

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Trp-ing upon new repressors

Posted on Feb 26th, 2018 - By Andreas K. Brödel

Trp-ing upon new repressorsTrp-ing upon new repressors, Published online: 26 February 2018; doi:10.1038/s41589-018-0012-9Bioengineers have used directed evolution to generate a new family of synthetic transcription factors based on the tryptophan repressor. The evolved repressor family enables researchers to build new gene circuits for biomedical…

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Directed evolution of a synthetic phylogeny of programmable Trp repressors

Posted on Feb 26th, 2018 - By Jared W. Ellefson

Directed evolution of a synthetic phylogeny of programmable Trp repressorsDirected evolution of a synthetic phylogeny of programmable Trp repressors, Published online: 26 February 2018; doi:10.1038/s41589-018-0006-7Directed evolution of Trp repressor (TrpR) variants that are responsive to halogenated tryptophan analogs and recognize new operator sites serve as useful components for constructing complex gene expression…

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Resistance to nonribosomal peptide antibiotics mediated by <span class=”small-caps”>d</span>-stereospecific peptidases

Posted on Feb 26th, 2018 - By Yong-Xin Li

Resistance to nonribosomal peptide antibiotics mediated by d-stereospecific peptidasesResistance to nonribosomal peptide antibiotics mediated by <span class="small-caps">d</span>-stereospecific peptidases, Published online: 26 February 2018; doi:10.1038/s41589-018-0009-4Networking-associated genome mining on bacterial genomes followed by chemical and enzymatic analysis identified a mechanism of resistance toward nonribosomal peptide antibiotics based on hydrolytic…

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A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters

Posted on Feb 26th, 2018 - By Kiryl D. Piatkevich

A robotic multidimensional directed evolution approach applied to fluorescent voltage reportersA robotic multidimensional directed evolution approach applied to fluorescent voltage reporters, Published online: 26 February 2018; doi:10.1038/s41589-018-0004-9Directed evolution of opsins via robotic high-content screening finds a fluorescent reporter of voltage that is simultaneously optimized for brightness, localization and voltage sensitivity and is applicable in three model…

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Oxidative demethylation of algal carbohydrates by cytochrome P450 monooxygenases

Posted on Feb 19th, 2018 - By Lukas Reisky

Oxidative demethylation of algal carbohydrates by cytochrome P450 monooxygenasesOxidative demethylation of algal carbohydrates by cytochrome P450 monooxygenases, Published online: 19 February 2018; doi:10.1038/s41589-018-0005-8The discovery of cytochrome P450 monooxygenases that catalyze oxidative demethylation of 6-O-methyl-d-galactose reveals a new activity of cytochrome P450 enzymes and their role in polysaccharide biomass degradation in marine…

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Viruses: Capsids under pressure

Posted on Feb 14th, 2018 - By Mirella Bucci

Viruses: Capsids under pressureViruses: Capsids under pressure, Published online: 14 February 2018; doi:10.1038/nchembio.2578Viruses: Capsids under…

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How many human proteoforms are there?

Posted on Feb 14th, 2018 - By Ruedi Aebersold

How many human proteoforms are there?How many human proteoforms are there?, Published online: 14 February 2018; doi:10.1038/nchembio.2576How many human proteoforms are…

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Insights into the biogenesis, function, and regulation of ADP-ribosylation

Posted on Feb 14th, 2018 - By Michael S Cohen

Insights into the biogenesis, function, and regulation of ADP-ribosylationInsights into the biogenesis, function, and regulation of ADP-ribosylation, Published online: 14 February 2018; doi:10.1038/nchembio.2568Insights into the biogenesis, function, and regulation of…

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RNA structure: A LASER-focused view into cells

Posted on Feb 14th, 2018 - By Philip C Bevilacqua

RNA structure: A LASER-focused view into cellsRNA structure: A LASER-focused view into cells, Published online: 14 February 2018; doi:10.1038/nchembio.2570RNA structure is irrevocably linked to function. A new method, termed 'LASER', utilizes a light-activated chemical probe to query RNA tertiary structure and illuminate RNA–protein interactions in the living…

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The ABCs of PTMs

Posted on Feb 14th, 2018 - By Karl W Barber

The ABCs of PTMsThe ABCs of PTMs, Published online: 14 February 2018; doi:10.1038/nchembio.2572Post-translational modifications (PTMs) are ubiquitous in all forms of life and often modulate critical protein functions. Recent chemical and biological advances have finally enabled scientists to precisely modify proteins at physiologically relevant positions, ushering in a new era of protein…

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Ubiquitination: Trashing the CIA

Posted on Feb 14th, 2018 - By Grant Miura

Ubiquitination: Trashing the CIAUbiquitination: Trashing the CIA, Published online: 14 February 2018; doi:10.1038/nchembio.2580Ubiquitination: Trashing the…

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Protein evolution: Hacking an enzyme

Posted on Feb 14th, 2018 - By Kristoffer E Johansson

Protein evolution: Hacking an enzymeProtein evolution: Hacking an enzyme, Published online: 14 February 2018; doi:10.1038/nchembio.2574Early stages of protein evolution are inherently difficult to study. Genetic selection in Escherichia coli has now identified a life-sustaining de novo enzyme arising from a simple scaffold that is completely different from the native…

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Altering form for function

Altering form for functionAltering form for function, Published online: 14 February 2018; doi:10.1038/nchembio.2582Elucidating the mechanisms by which biomolecules are chemically modified and how these alterations regulate biological pathways represents a leading frontier in chemical…

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Partial DNA-guided Cas9 enables genome editing with reduced off-target activity

Posted on Jan 29th, 2018 - By Hao Yin

Partial DNA-guided Cas9 enables genome editing with reduced off-target activityPartial DNA-guided Cas9 enables genome editing with reduced off-target activity, Published online: 29 January 2018; doi:10.1038/nchembio.2559Partial substitution of CRISPR RNAs with DNA nucleotides retains CRISPR–Cas9 genome editing activity while enhancing efficiency and specificity within cells, suggesting that DNA–RNA hybrids may be economical reagents for targeted genome…

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Rewiring T-cell responses to soluble factors with chimeric antigen receptors

Posted on Jan 29th, 2018 - By ZeNan L Chang

Rewiring T-cell responses to soluble factors with chimeric antigen receptorsRewiring T-cell responses to soluble factors with chimeric antigen receptors, Published online: 29 January 2018; doi:10.1038/nchembio.2565Chimeric antigen receptor (CAR)-expressing T cells were engineered to recognize soluble protein ligands that, by inducing CAR dimerization, mechanically couple ligand binding and receptor signaling to produce immune effector…

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Lytic xylan oxidases from wood-decay fungi unlock biomass degradation

Posted on Jan 29th, 2018 - By Marie Couturier

Lytic xylan oxidases from wood-decay fungi unlock biomass degradationLytic xylan oxidases from wood-decay fungi unlock biomass degradation, Published online: 29 January 2018; doi:10.1038/nchembio.2558A new type of fungal lytic polysaccharide monooxygenase (LPMO) catalyzes the oxidative degradation of xylan components of cellulosic biomass and offers potential in wood…

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A whole-animal platform to advance a clinical kinase inhibitor into new disease space

Posted on Jan 22nd, 2018 - By Masahiro Sonoshita

A whole-animal platform to advance a clinical kinase inhibitor into new disease spaceA whole-animal platform to advance a clinical kinase inhibitor into new disease space, Published online: 22 January 2018; doi:10.1038/nchembio.2556Combining Drosophila genetics with chemistry and computation led to the development of novel kinase inhibitors based on the RAF-targeting drug sorafenib that reveal the RET oncogene as an enhancer of drug action and improve the therapeutic window in medullary thyroid…

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Chemical hijacking of auxin signaling with an engineered auxin–TIR1 pair

Posted on Jan 22nd, 2018 - By Naoyuki Uchida

Chemical hijacking of auxin signaling with an engineered auxin–TIR1 pairChemical hijacking of auxin signaling with an engineered auxin–TIR1 pair, Published online: 22 January 2018; doi:10.1038/nchembio.2555A synthetic, orthogonal pair of the plant hormone auxin and its receptor TIR1 was engineered to hijack auxin signaling without interfering with the endogenous system. The synthetic system conclusively demonstrates the role for TIR1 in auxin-induced acid…

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Toward an orthogonal central dogma

Posted on Jan 16th, 2018 - By Chang C Liu

Toward an orthogonal central dogmaToward an orthogonal central dogma, Published online: 16 January 2018; doi:10.1038/nchembio.2554The central dogma processes of DNA replication, transcription, and translation are responsible for the maintenance and expression of every gene in an organism. An orthogonal central dogma may insulate genetic programs from host regulation and allow expansion of the roles of these processes within the…

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Cell biology: Eaten up from the inside

Posted on Jan 16th, 2018 - By Karin Kuehnel

Cell biology: Eaten up from the insideCell biology: Eaten up from the inside, Published online: 16 January 2018; doi:10.1038/nchembio.2563Cell biology: Eaten up from the…

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Plant hormones: Metabolic end run to jasmonate

Posted on Jan 16th, 2018 - By Gregg A Howe

Plant hormones: Metabolic end run to jasmonatePlant hormones: Metabolic end run to jasmonate, Published online: 16 January 2018; doi:10.1038/nchembio.2553The lipid-derived hormone jasmonate promotes durable resistance of plants to a myriad of herbivores and pathogens. New evidence reveals an alternative pathway for the terminal steps of jasmonate biosynthesis and further advances our understanding of bioactive oxylipins in the plant…

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RNA Splicing: Making the cut

Posted on Jan 16th, 2018 - By Stéphane Larochelle

RNA Splicing: Making the cutRNA Splicing: Making the cut, Published online: 16 January 2018; doi:10.1038/nchembio.2564RNA Splicing: Making the…

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Drug development: Allosteric inhibitors hit USP7 hard

Posted on Jan 16th, 2018 - By Wei Zhang

Drug development: Allosteric inhibitors hit USP7 hardDrug development: Allosteric inhibitors hit USP7 hard, Published online: 16 January 2018; doi:10.1038/nchembio.2557A potent and specific small-molecule inhibitor of a long-sought-after anticancer drug target, USP7, that acts allosterically to inhibit MDM2-stabilizing activity foretells of more allosteric inhibitors for deubiquitinases and E3…

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Errata: Continuous directed evolution of aminoacyl-tRNA synthetases

Posted on Jan 16th, 2018 - By David I Bryson

Errata: Continuous directed evolution of aminoacyl-tRNA synthetasesErrata: Continuous directed evolution of aminoacyl-tRNA synthetases, Published online: 16 January 2018; doi:10.1038/nchembio0218-186Errata: Continuous directed evolution of aminoacyl-tRNA…

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Synthetic biology: License to kill

Posted on Jan 16th, 2018 - By Caitlin Deane

Synthetic biology: License to killSynthetic biology: License to kill, Published online: 16 January 2018; doi:10.1038/nchembio.2561Synthetic biology: License to…

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Natural products: Tapping into personalized chemistry

Posted on Jan 16th, 2018 - By Jack R Davison

Natural products: Tapping into personalized chemistryNatural products: Tapping into personalized chemistry, Published online: 16 January 2018; doi:10.1038/nchembio.2560By integrating metagenomics, spectroscopy and synthetic biology, the individualized chemistry of small reef-dwelling organisms and their associated microbiota can be characterized in exquisite detail, unlocking a wealth of structural diversity for the development of new…

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Na<sup>+</sup>-mimicking ligands stabilize the inactive state of leukotriene B<sub>4</sub> receptor BLT1

Posted on Jan 8th, 2018 - By Tetsuya Hori

Na+-mimicking ligands stabilize the inactive state of leukotriene B4 receptor BLT1Na<sup>+</sup>-mimicking ligands stabilize the inactive state of leukotriene B<sub>4</sub> receptor BLT1, Published online: 08 January 2018; doi:10.1038/nchembio.2547A structure of leukotriene B4 receptor BLT1 bound with a benzamidine-containing compound, BIIL260, reveals an inverse-agonist mechanism involving ligand binding in the sodium ion-centered water cluster adjacent to the conserved…

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Mechanism of intersubunit ketosynthase–dehydratase interaction in polyketide synthases

Posted on Jan 8th, 2018 - By Matthew Jenner

Mechanism of intersubunit ketosynthase–dehydratase interaction in polyketide synthasesMechanism of intersubunit ketosynthase–dehydratase interaction in polyketide synthases, Published online: 08 January 2018; doi:10.1038/nchembio.2549A combination of biochemical and structural techniques allows the characterization of a novel docking domain in polyketide synthases, which is structurally disordered and facilitates association of subunits at ketosynthase–dehydratase…

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Employing a biochemical protecting group for a sustainable indigo dyeing strategy

Posted on Jan 8th, 2018 - By Tammy M Hsu

Employing a biochemical protecting group for a sustainable indigo dyeing strategyEmploying a biochemical protecting group for a sustainable indigo dyeing strategy, Published online: 08 January 2018; doi:10.1038/nchembio.2552An environmentally friendly approach to indigo production is facilitated by the characterization of a plant indoxyl glucosyltransferase, which converts the unstable indoxyl precursor into indican by addition of a glucose protecting…

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An OPR3-independent pathway uses 4,5-didehydrojasmonate for jasmonate synthesis

Posted on Jan 1st, 2018 - By Andrea Chini

An OPR3-independent pathway uses 4,5-didehydrojasmonate for jasmonate synthesisAn OPR3-independent pathway uses 4,5-didehydrojasmonate for jasmonate synthesis, Published online: 01 January 2018; doi:10.1038/nchembio.2540OPR3 is required to reduce the JA-Ile precursor OPDA. Analyses of JA levels in a loss-of-function opr3-3 mutant identified an OPR3-independent pathway for JA-Ile biosynthesis, based on OPDA conversion to 4,5-ddh-JA and reduction to JA by…

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Accessing chemical diversity from the uncultivated symbionts of small marine animals

Posted on Jan 1st, 2018 - By Thomas E Smith

Accessing chemical diversity from the uncultivated symbionts of small marine animalsAccessing chemical diversity from the uncultivated symbionts of small marine animals, Published online: 01 January 2018; doi:10.1038/nchembio.2537A combination of spectroscopy, metagenomics, and synthetic biology enables the characterization of the antiviral divamides, a class of lanthipeptide natural products in which even minor changes in structure lead to different biological…

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A role for 2-Cys peroxiredoxins in facilitating cytosolic protein thiol oxidation

Posted on Dec 18th, 2017 - By Sarah Stöcker

A role for 2-Cys peroxiredoxins in facilitating cytosolic protein thiol oxidationA role for 2-Cys peroxiredoxins in facilitating cytosolic protein thiol oxidation, Published online: 18 December 2017; doi:10.1038/nchembio.2536Cytosolic 2-Cys peroxiredoxins can enable, rather than compete with, rapid thiol oxidation by relaying H2O2-derived oxidizing equivalents to other proteins, suggesting a broadened role for peroxiredoxins as sensors and transmitters of H2O2…

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Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation

Posted on Dec 18th, 2017 - By Calla M Olson

Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradationPharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation, Published online: 18 December 2017; doi:10.1038/nchembio.2538A selective small-molecule degrader of CDK9 was generated by conjugating an imide to SNS-032, a promiscuous ATP-site-directed CDK binder. The pharmacological consequences of CDK9 degradation versus inhibition were…

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Expression system for structural and functional studies of human glycosylation enzymes

Posted on Dec 18th, 2017 - By Kelley W Moremen

Expression system for structural and functional studies of human glycosylation enzymesExpression system for structural and functional studies of human glycosylation enzymes, Published online: 18 December 2017; doi:10.1038/nchembio.2539A modular protein expression system enables the structural and functional characterization of human glycosyltransferases, glycoside hydrolases and other carbohydrate-modifying…

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Neurobiology: Defining your territory

Posted on Dec 12th, 2017 - By Grant Miura

Neurobiology: Defining your territoryNeurobiology: Defining your territory, Published online: 12 December 2017; doi:10.1038/nchembio.2544Neurobiology: Defining your…

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RNA modifications: Ribosomes get decorated

Posted on Dec 12th, 2017 - By Mirella Bucci

RNA modifications: Ribosomes get decoratedRNA modifications: Ribosomes get decorated, Published online: 12 December 2017; doi:10.1038/nchembio.2543RNA modifications: Ribosomes get…

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Notch signaling: A sweet strategy

Posted on Dec 12th, 2017 - By Tetsuya Okajima

Notch signaling: A sweet strategyNotch signaling: A sweet strategy, Published online: 12 December 2017; doi:10.1038/nchembio.2532Glycosylation of Notch receptors regulates ligand-induced Notch signaling, which is essential for normal development in animals. Fucose analogs targeting Notch glycosylation serve as ligand-specific Notch inhibitors and facilitate the understanding of how O-glycan regulates Notch–ligand…

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Microbiology: Trapping Rac1

Posted on Dec 12th, 2017 - By Karin Kuehnel

Microbiology: Trapping Rac1Microbiology: Trapping Rac1, Published online: 12 December 2017; doi:10.1038/nchembio.2541Microbiology: Trapping…

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Resistance mechanisms: Watering down a warhead

Posted on Dec 12th, 2017 - By Caitlin Deane

Resistance mechanisms: Watering down a warheadResistance mechanisms: Watering down a warhead, Published online: 12 December 2017; doi:10.1038/nchembio.2542Resistance mechanisms: Watering down a…

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Protein engineering: Finding the best ligase

Posted on Dec 12th, 2017 - By Christian F W Becker

Protein engineering: Finding the best ligaseProtein engineering: Finding the best ligase, Published online: 12 December 2017; doi:10.1038/nchembio.2533Modification of folded proteins at will, within any sequence context, remains an elusive goal. A proteome-wide screening approach has now identified a set of protein ligases that enables conjugation of peptides to almost any protein N terminus, overcoming longstanding limitations in protein…

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Structure-inspired design of β-arrestin-biased ligands for aminergic GPCRs

Posted on Dec 11th, 2017 - By John D McCorvy

Structure-inspired design of β-arrestin-biased ligands for aminergic GPCRsStructure-inspired design of β-arrestin-biased ligands for aminergic GPCRs, Published online: 11 December 2017; doi:10.1038/nchembio.2527Development of D2 dopamine receptor ligands biased for β-arrestin recruitment based on a receptor homology model that identified conserved ligand contacts within the TM5 and EL2 regions as important for biased…

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Engineered synthetic scaffolds for organizing proteins within the bacterial cytoplasm

Posted on Dec 11th, 2017 - By Matthew J Lee

Engineered synthetic scaffolds for organizing proteins within the bacterial cytoplasmEngineered synthetic scaffolds for organizing proteins within the bacterial cytoplasm, Published online: 11 December 2017; doi:10.1038/nchembio.2535Two complementary coiled-coil peptides and a bacterial microcompartment shell protein are combined to construct cytoscaffolds within Escherichia coli cells. Targeting enzymes to the cytoplasmic scaffold results in colocalization and improved metabolic…

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Human antibody-based chemically induced dimerizers for cell therapeutic applications

Posted on Dec 4th, 2017 - By Zachary B Hill

Human antibody-based chemically induced dimerizers for cell therapeutic applicationsHuman antibody-based chemically induced dimerizers for cell therapeutic applications, Published online: 04 December 2017; doi:10.1038/nchembio.2529Selections with a phage-displayed antibody library against an existing protein–small-molecule complex enabled the generation of antibody-based chemically induced dimerizers (AbCIDs) with the properties necessary for use in regulating cell…

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Discovery and characterization of highly potent and selective allosteric USP7 inhibitors

Posted on Dec 4th, 2017 - By Gerald Gavory

Discovery and characterization of highly potent and selective allosteric USP7 inhibitorsDiscovery and characterization of highly potent and selective allosteric USP7 inhibitors, Published online: 04 December 2017; doi:10.1038/nchembio.2528A selective inhibitor of the deubiquitinase USP7 binds an allosteric site to inhibit its MDM2-stabilizing activity, resulting in stabilization of p53 and p21, which confers hypersensitivity to cancer cells for killing by the…

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Inhibition of Delta-induced Notch signaling using fucose analogs

Posted on Nov 27th, 2017 - By Michael Schneider

Inhibition of Delta-induced Notch signaling using fucose analogsInhibition of Delta-induced Notch signaling using fucose analogs, Published online: 27 November 2017; doi:10.1038/nchembio.2520Protein O-fucosyltransferase 1 (Pofut1) regulates Notch activity by adding O-fucose residues to its extracellular domain. Fucose analogs were identified that inhibited Delta-mediated Notch binding and activation but spared Jagged1-mediated…

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5-Formylcytosine to cytosine conversion by C–C bond cleavage <i>in vivo</i>

Posted on Nov 27th, 2017 - By Katharina Iwan

5-Formylcytosine to cytosine conversion by C–C bond cleavage in vivo5-Formylcytosine to cytosine conversion by C–C bond cleavage <i>in vivo</i>, Published online: 27 November 2017; doi:10.1038/nchembio.2531Direct conversion of 5-fdC into dC by C–C bond breakage is revealed by metabolic tracing studies through incorporation of synthetic stable isotope- and (R)-2′-fluorine-labeled dC and fdC derivatives into the genome of cultured mammalian…

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Host–pathogen interactions: A ubiquitin defense

Posted on Nov 21st, 2017 - By Mirella Bucci

Host–pathogen interactions: A ubiquitin defenseHost–pathogen interactions: A ubiquitin defense, Published online: 21 November 2017; doi:10.1038/nchembio.2524Host–pathogen interactions: A ubiquitin…

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Enzymology: I want my cluster back

Posted on Nov 21st, 2017 - By Caitlin Deane

Enzymology: I want my cluster backEnzymology: I want my cluster back, Published online: 21 November 2017; doi:10.1038/nchembio.2525Enzymology: I want my cluster…

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Peptide design: Hacking hemagglutinin

Posted on Nov 21st, 2017 - By Karin Kuehnel

Peptide design: Hacking hemagglutininPeptide design: Hacking hemagglutinin, Published online: 21 November 2017; doi:10.1038/nchembio.2523Peptide design: Hacking…

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Errata: Functional annotation of chemical libraries across diverse biological processes

Posted on Nov 21st, 2017 - By Jeff S Piotrowski

Errata: Functional annotation of chemical libraries across diverse biological processesErrata: Functional annotation of chemical libraries across diverse biological processes, Published online: 21 November 2017; doi:10.1038/nchembio1217-1286aErrata: Functional annotation of chemical libraries across diverse biological…

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Errata: Functional annotation of chemical libraries across diverse biological processes

Posted on Nov 21st, 2017 - By Jeff S Piotrowski

Errata: Functional annotation of chemical libraries across diverse biological processesErrata: Functional annotation of chemical libraries across diverse biological processes, Published online: 21 November 2017; doi:10.1038/nchembio1217-1286bErrata: Functional annotation of chemical libraries across diverse biological…

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Genetic code expansion: Synthetases pick up the PACE

Posted on Nov 21st, 2017 - By Jeffery M Tharp

Genetic code expansion: Synthetases pick up the PACEGenetic code expansion: Synthetases pick up the PACE, Published online: 21 November 2017; doi:10.1038/nchembio.2516Phage-assisted evolution can rapidly improve the efficiency and substrate specificity of orthogonal aminoacyl-tRNA synthetases. Furthermore, the crystal structure of the pyrrolysyl-tRNA synthetase N-terminal domain reveals the basis for these improvements and provides a structural rationale for…

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Nucleic acids: mRNAs get a TREAT

Posted on Nov 21st, 2017 - By Grant Miura

Nucleic acids: mRNAs get a TREATNucleic acids: mRNAs get a TREAT, Published online: 21 November 2017; doi:10.1038/nchembio.2522Nucleic acids: mRNAs get a…

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Cancer systems biology: Harnessing off-target effects

Posted on Nov 21st, 2017 - By Gaye Saginc

Cancer systems biology: Harnessing off-target effectsCancer systems biology: Harnessing off-target effects, Published online: 21 November 2017; doi:10.1038/nchembio.2519The 'off-targets' of a drug are often poorly characterized yet could be harnessed in the treatment of complex diseases. A recent study used a small-molecule screening in non-small-cell lung cancer to repurpose an FDA-approved ALK/IGF1R inhibitor and uncover its mechanism of…

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Monobactam formation in sulfazecin by a nonribosomal peptide synthetase thioesterase

Posted on Nov 20th, 2017 - By Ryan A Oliver

Monobactam formation in sulfazecin by a nonribosomal peptide synthetase thioesteraseMonobactam formation in sulfazecin by a nonribosomal peptide synthetase thioesterase, Published online: 20 November 2017; doi:10.1038/nchembio.2526Biosynthesis of the antibiotic sulfazecin involves N-sulfonation in trans of the tripeptide intermediate before synthesis of the β-lactam ring by a noncanonical thioesterase domain, demonstrating a new enzymatic route to the azetidinone…

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Engineering peptide ligase specificity by proteomic identification of ligation sites

Posted on Nov 20th, 2017 - By Amy M Weeks

Engineering peptide ligase specificity by proteomic identification of ligation sitesEngineering peptide ligase specificity by proteomic identification of ligation sites, Published online: 20 November 2017; doi:10.1038/nchembio.2521A comprehensive characterization of peptide ligase specificity using proteome-derived peptide libraries enables the identification of 72 new subtiligases and their application to site-specific bioconjugation and sequencing of the cellular N…

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Small-molecule inhibition of TLR8 through stabilization of its resting state

Posted on Nov 20th, 2017 - By Shuting Zhang

Small-molecule inhibition of TLR8 through stabilization of its resting stateSmall-molecule inhibition of TLR8 through stabilization of its resting state, Published online: 20 November 2017; doi:10.1038/nchembio.2518High-throughput screening identified potent small-molecule inhibitors of the endosomal Toll-like receptor TLR8 that stabilize the preformed TLR8 dimer in its resting state by binding to a unique site on the inactive dimer…

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Top-down characterization of endogenous protein complexes with native proteomics

Posted on Nov 13th, 2017 - By Owen S Skinner

Top-down characterization of endogenous protein complexes with native proteomicsTop-down characterization of endogenous protein complexes with native proteomics, Published online: 13 November 2017; doi:10.1038/nchembio.2515NatureArticleSnippet(type=short-summary, markup=A multistage tandem mass spectrometry approach enables the application of native proteomics to characterize intact endogenous protein complexes in discovery mode, including covalent modifications as well as noncovalently bound…

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Metabolomics-based discovery of a metabolite that enhances oligodendrocyte maturation

Posted on Nov 13th, 2017 - By Brittney A Beyer

Metabolomics-based discovery of a metabolite that enhances oligodendrocyte maturationMetabolomics-based discovery of a metabolite that enhances oligodendrocyte maturation, Published online: 13 November 2017; doi:10.1038/nchembio.2517NatureArticleSnippet(type=short-summary, markup=Mass-spectrometry-based metabolomics analysis of oligodendrocyte differentiation led to the identification of an endogenous metabolite, taurine, that enhanced the process of drug-induced OPC differentiation.,…

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Synthetic microbial consortia enable rapid assembly of pure translation machinery

Posted on Nov 13th, 2017 - By Fernando Villarreal

Synthetic microbial consortia enable rapid assembly of pure translation machinerySynthetic microbial consortia enable rapid assembly of pure translation machinery, Published online: 13 November 2017; doi:10.1038/nchembio.2514NatureArticleSnippet(type=short-summary, markup=Strains of Escherichia coli, each expressing a subset of the 34 translation machinery proteins, are grown in synthetic microbial consortia to enable the efficient isolation of the full machinery from a single culturing, lysis,…

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Nonimmune cells equipped with T-cell-receptor-like signaling for cancer cell ablation

Posted on Nov 13th, 2017 - By Ryosuke Kojima

Nonimmune cells equipped with T-cell-receptor-like signaling for cancer cell ablationNonimmune cells equipped with T-cell-receptor-like signaling for cancer cell ablation, Published online: 13 November 2017; doi:10.1038/nchembio.2498NatureArticleSnippet(type=short-summary, markup=Engineering of nonimmune cells with a cell-contact sensor and antigen recognition domains enables cell-contact-dependent sensor cell signaling and effector molecule production directed to attack target cells, providing…

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Ultrasensitive optical imaging with lanthanide lumiphores

Posted on Nov 6th, 2017 - By Ukrae Cho

Ultrasensitive optical imaging with lanthanide lumiphoresUltrasensitive optical imaging with lanthanide lumiphores, Published online: 06 November 2017; doi:10.1038/nchembio.2513NatureArticleSnippet(type=short-summary, markup=Ultrasensitive imaging of lanthanide chelates is achieved by integrating transreflected illumination, luminescence resonance energy transfer, and time-resolved microscopy.,…

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Purinyl-cobamide is a native prosthetic group of reductive dehalogenases

Posted on Nov 6th, 2017 - By Jun Yan

Purinyl-cobamide is a native prosthetic group of reductive dehalogenasesPurinyl-cobamide is a native prosthetic group of reductive dehalogenases, Published online: 06 November 2017; doi:10.1038/nchembio.2512NatureArticleSnippet(type=short-summary, markup=In organohalide-respiring bacteria, reductive dehalogenases cleave carbon–halogen bonds using cobamide prosthetic groups. Desulfitobacterium hafniense uses an unprecedented cobamide variant, which includes unsubstituted purine, for this…

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Synthetic beta cells for fusion-mediated dynamic insulin secretion

Posted on Oct 30th, 2017 - By Zhaowei Chen

Synthetic beta cells for fusion-mediated dynamic insulin secretionSynthetic beta cells for fusion-mediated dynamic insulin secretion, Published online: 30 October 2017; doi:10.1038/nchembio.2511NatureArticleSnippet(type=short-summary, markup=Synthetic beta cells were fabricated through 'vesicles-in-vesicle' liposomal superstructures equipped with glucose-sensing and membrane-fusion machinery, thus enabling sensing of graded glucose levels and secretion of insulin via fusion processes.,…

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PatB1 is an <i>O</i>-acetyltransferase that decorates secondary cell wall polysaccharides

Posted on Oct 30th, 2017 - By David Sychantha

PatB1 is an O-acetyltransferase that decorates secondary cell wall polysaccharidesPatB1 is an <i>O</i>-acetyltransferase that decorates secondary cell wall polysaccharides, Published online: 30 October 2017; doi:10.1038/nchembio.2509NatureArticleSnippet(type=short-summary, markup=A chemically synthesized analog of Bacillus cereus secondary cell wall polysaccharide (SCWP) facilitates the identification of PatB1 as a SCWP O-acetyltransferase, and the structure of PatB1 provides…

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Small molecule promotes β-catenin citrullination and inhibits Wnt signaling in cancer

Posted on Oct 30th, 2017 - By Yi Qu

Small molecule promotes β-catenin citrullination and inhibits Wnt signaling in cancerSmall molecule promotes β-catenin citrullination and inhibits Wnt signaling in cancer, Published online: 30 October 2017; doi:10.1038/nchembio.2510NatureArticleSnippet(type=short-summary, markup=The small molecule nitazoxanide (NTZ) was identified as a Wnt inhibitor by promoting protein citrullination of β-catenin through increased cytosolic calcium and PAD2 protein stabilization. β-catenin citrullination…

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Electrophilic probes for deciphering substrate recognition by O-GlcNAc transferase

Posted on Oct 23rd, 2017 - By Chia-Wei Hu

Electrophilic probes for deciphering substrate recognition by O-GlcNAc transferaseElectrophilic probes for deciphering substrate recognition by O-GlcNAc transferase, Published online: 23 October 2017; doi:10.1038/nchembio.2494NatureArticleSnippet(type=short-summary, markup=N-Acetylglucosamine derivatives equipped with electrophilic groups and handles for subsequent chemical tagging are useful probes of substrate recognition by O-GlcNAc transferases and enable the capture of transient protein…

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