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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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Rational design of proteins that exchange on functional timescales

Posted on Oct 23rd, 2017 - By James A Davey

Rational design of proteins that exchange on functional timescalesRational design of proteins that exchange on functional timescales, Published online: 23 October 2017; doi:10.1038/nchembio.2503NatureArticleSnippet(type=short-summary, markup=The development of a computational protein design method, meta-multistate design, enables the design and validation of protein variants termed DANCERs that spontaneously exchange between predicted conformational states on the millisecond timescale.,…

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A CRISPR screen identifies a pathway required for paraquat-induced cell death

Posted on Oct 23rd, 2017 - By Colleen R Reczek

A CRISPR screen identifies a pathway required for paraquat-induced cell deathA CRISPR screen identifies a pathway required for paraquat-induced cell death, Published online: 23 October 2017; doi:10.1038/nchembio.2499NatureArticleSnippet(type=short-summary, markup=A positive-selection CRISPR screen with the pro-oxidant paraquat (PQ) uncovers three genes mediating PQ-induced cell death: POR is the source of PQ-mediated reactive oxygen species (ROS) generation, and ATP7A and SLC45A4 promote…

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Bacterial cell wall: Phages breaking free

Posted on Oct 18th, 2017 - By Karin Kuehnel

Bacterial cell wall: Phages breaking freeNature Chemical Biology, Published online: 18 October 2017;…

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Biomaterials: Cotton gets superpowers

Posted on Oct 18th, 2017 - By Caitlin Deane

Biomaterials: Cotton gets superpowersNature Chemical Biology, Published online: 18 October 2017;…

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Host-microbe interactions: Aiming at GPCRs

Posted on Oct 18th, 2017 - By Mirella Bucci

Host-microbe interactions: Aiming at GPCRsNature Chemical Biology, Published online: 18 October 2017;…

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Drug discovery: Controlling protein SUMOylation

Posted on Oct 18th, 2017 - By John S Schneekloth Jr

Drug discovery: Controlling protein SUMOylationNature Chemical Biology, Published online: 18 October 2017; doi:10.1038/nchembio.2496A potent and selective inhibitor of protein SUMOylation, a ubiquitin-like post-translational modification, has been developed, shedding light on the potential for developing new classes of anticancer…

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Ubiquitin biology: Unraveling the chain

Posted on Oct 18th, 2017 - By Grant Miura

Ubiquitin biology: Unraveling the chainNature Chemical Biology, Published online: 18 October 2017;…

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Chemical methods: DREADDs see no CNO

Posted on Sep 19th, 2017 - By Mirella Bucci

Nature Chemical Biology 13, 1057 (2017). doi:10.1038/nchembio.2483 Author: Mirella…

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Protein engineering: Expanding splicing versatility

Posted on Sep 19th, 2017 - By Karin Kuehnel

Nature Chemical Biology 13, 1057 (2017). doi:10.1038/nchembio.2485 Author: Karin…

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Bioorthogonal chemistry: Click on, click off

Posted on Sep 19th, 2017 - By Caitlin Deane

Nature Chemical Biology 13, 1057 (2017). doi:10.1038/nchembio.2482 Author: Caitlin…

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Developmental signaling: Peaking early

Posted on Sep 19th, 2017 - By Grant Miura

Nature Chemical Biology 13, 1057 (2017). doi:10.1038/nchembio.2484 Author: Grant…

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Target class drug discovery

Posted on Sep 19th, 2017 - By Kimberly D Barnash

Nature Chemical Biology 13, 1053 (2017). doi:10.1038/nchembio.2473 Authors: Kimberly D Barnash, Lindsey I James & Stephen V Frye Selection of molecular targets based on disease understanding is a dominant paradigm in drug discovery. We argue that a focus on classes of targets with central roles in biology provides a complimentary approach that has higher quality outcomes in early discovery…

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Genome mining: Digging the tunnel for chemical space

Posted on Sep 19th, 2017 - By Ha An Nguyen

Nature Chemical Biology 13, 1061 (2017). doi:10.1038/nchembio.2480 Authors: Ha An Nguyen & Christine M Dunham Genome mining reveals a new ribosomally synthesized and post-translationally modified peptide (RiPP) from Klebsiella pneumoniae. This new antibiotic inhibits bacterial ribosomes by obstructing the peptide exit tunnel, and its modular nature presents a unique opportunity for future engineering of antibacterial…

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Biosynthesis: SAM cycles up for colibactin

Posted on Sep 19th, 2017 - By Steven G Van Lanen

Nature Chemical Biology 13, 1059 (2017). doi:10.1038/nchembio.2479 Author: Steven G Van Lanen The introduction of a cyclopropyl group is critical for imparting colibactin with the ability to cleave DNA. Nonribosomal peptide synthetase ClbH and polyketide synthase ClbI are now shown to work in concert to convert S-adenosylmethionine into this cyclopropyl…

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Erratum: A Vibrio cholerae autoinducer–receptor pair that controls biofilm formation

Posted on Sep 19th, 2017 - By Kai Papenfort

Nature Chemical Biology 13, 1137 (2017). doi:10.1038/nchembio1017-1137a Author: Kai Papenfort, Justin E Silpe, Kelsey R Schramma, Jian-Ping Cong, Mohammad R Seyedsayamdost & Bonnie L…

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Corrigendum: Parallel evolution of non-homologous isofunctional enzymes in methionine biosynthesis

Posted on Sep 19th, 2017 - By Karine Bastard

Nature Chemical Biology 13, 1137 (2017). doi:10.1038/nchembio1017-1137c Author: Karine Bastard, Alain Perret, Aline Mariage, Thomas Bessonnet, Agnès Pinet-Turpault, Jean-Louis Petit, Ekaterina Darii, Pascal Bazire, Carine Vergne-Vaxelaire, Clémence Brewee, Adrien Debard, Virginie Pellouin, Marielle Besnard-Gonnet, François Artiguenave, Claudine Médigue, David Vallenet, Antoine Danchin, Anne Zaparucha, Jean Weissenbach, Marcel Salanoubat & Véronique de…

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Erratum: A Vibrio cholerae autoinducer–receptor pair that controls biofilm formation

Posted on Sep 19th, 2017 - By Kai Papenfort

Nature Chemical Biology 13, 1137 (2017). doi:10.1038/nchembio1017-1137b Author: Kai Papenfort, Justin E Silpe, Kelsey R Schramma, Jian-Ping Cong, Mohammad R Seyedsayamdost & Bonnie L…

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Klebsazolicin inhibits 70S ribosome by obstructing the peptide exit tunnel

Posted on Aug 28th, 2017 - By Mikhail Metelev

Nature Chemical Biology 13, 1129 (2017). doi:10.1038/nchembio.2462 Authors: Mikhail Metelev, Ilya A Osterman, Dmitry Ghilarov, Nelli F Khabibullina, Alexander Yakimov, Konstantin Shabalin, Irina Utkina, Dmitry Y Travin, Ekaterina S Komarova, Marina Serebryakova, Tatyana Artamonova, Mikhail Khodorkovskii, Andrey L Konevega, Petr V Sergiev, Konstantin Severinov & Yury S…

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Oxidative cleavage of polysaccharides by monocopper enzymes depends on H2O2

Posted on Aug 28th, 2017 - By Bastien Bissaro

Nature Chemical Biology 13, 1123 (2017). doi:10.1038/nchembio.2470 Authors: Bastien Bissaro, Åsmund K Røhr, Gerdt Müller, Piotr Chylenski, Morten Skaugen, Zarah Forsberg, Svein J Horn, Gustav Vaaje-Kolstad & Vincent G H…

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Metals induce transient folding and activation of the twister ribozyme

Posted on Aug 21st, 2017 - By Subrata Panja

Nature Chemical Biology 13, 1109 (2017). doi:10.1038/nchembio.2459 Authors: Subrata Panja, Boyang Hua, Diego Zegarra, Taekjip Ha & Sarah A…

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Crystal structures of trimeric HIV envelope with entry inhibitors BMS-378806 and BMS-626529

Posted on Aug 21st, 2017 - By Marie Pancera

Nature Chemical Biology 13, 1115 (2017). doi:10.1038/nchembio.2460 Authors: Marie Pancera, Yen-Ting Lai, Tatsiana Bylund, Aliaksandr Druz, Sandeep Narpala, Sijy O'Dell, Arne Schön, Robert T Bailer, Gwo-Yu Chuang, Hui Geng, Mark K Louder, Reda Rawi, Djade I Soumana, Andrés Finzi, Alon Herschhorn, Navid Madani, Joseph Sodroski, Ernesto Freire, David R Langley, John R Mascola, Adrian B McDermott & Peter D…

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Protein design: I like to fold it, fold it

Posted on Aug 18th, 2017 - By Caitlin Deane

Nature Chemical Biology 13, 923 (2017). doi:10.1038/nchembio.2467 Author: Caitlin…

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Neurobiology: Lighting up neurons

Posted on Aug 18th, 2017 - By Grant Miura

Nature Chemical Biology 13, 923 (2017). doi:10.1038/nchembio.2469 Author: Grant…

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Bacterial immunity: A virtuous CRISPR cycle

Posted on Aug 18th, 2017 - By Terry L. Sheppard

Nature Chemical Biology 13, 923 (2017). doi:10.1038/nchembio.2468 Author: Terry L.…

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Drug development: Locking down metabolism

Posted on Aug 18th, 2017 - By William R Bishai

Nature Chemical Biology 13, 925 (2017). doi:10.1038/nchembio.2452 Author: William R Bishai An allosteric inhibitor of Mycobacterium tuberculosis tryptophan synthase—an enzyme that is nonessential for in vitro growth—has potent antimicrobial activity, revealing a potentially expanded target list for antimicrobials and greater chemical space for new…

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A kinetic view of GPCR allostery and biased agonism

Posted on Aug 18th, 2017 - By J Robert Lane

Nature Chemical Biology 13, 929 (2017). doi:10.1038/nchembio.2431 Authors: J Robert Lane, Lauren T May, Robert G Parton, Patrick M Sexton & Arthur…

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Ubiquitin-proteasome system: Rescuing EBV latency

Posted on Aug 18th, 2017 - By Mirella Bucci

Nature Chemical Biology 13, 923 (2017). doi:10.1038/nchembio.2466 Author: Mirella…

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Protein engineering: Redirecting membrane machinery

Posted on Aug 18th, 2017 - By Kalistyn Burley

Nature Chemical Biology 13, 927 (2017). doi:10.1038/nchembio.2451 Authors: Kalistyn Burley & Celia W Goulding The ability to solubilize membrane proteins while retaining their native function is a persistent challenge. Re-engineering of the membrane protein DsbB into a soluble cytoplasmic version maintained its activity and enabled recompartmentalization of the periplasmic DsbAB disulfide bond–forming…

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Extracellular vesicles: Taking metabolism on the road

Posted on Aug 18th, 2017 - By Lucas B Sullivan

Nature Chemical Biology 13, 924 (2017). doi:10.1038/nchembio.2455 Author: Lucas B Sullivan Extracellular vesicles (EVs) are a class of secreted membrane particles capable of transferring biological molecules between cells. Metabolomics measurements indicate that isolated EVs also have autonomous metabolic enzyme activities, including the unexpected identification of endogenous human asparaginase…

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Small-molecule studies identify CDK8 as a regulator of IL-10 in myeloid cells

Posted on Aug 14th, 2017 - By Liv Johannessen

Nature Chemical Biology 13, 1102 (2017). doi:10.1038/nchembio.2458 Authors: Liv Johannessen, Thomas B Sundberg, Daniel J O'Connell, Raivo Kolde, James Berstler, Katelyn J Billings, Bernard Khor, Brinton Seashore-Ludlow, Anne Fassl, Caitlin N Russell, Isabel J Latorre, Baishan Jiang, Daniel B Graham, Jose R Perez, Piotr Sicinski, Andrew J Phillips, Stuart L Schreiber, Nathanael S Gray, Alykhan F Shamji & Ramnik J…

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Optogenetic control of kinetochore function

Posted on Aug 14th, 2017 - By Huaiying Zhang

Nature Chemical Biology 13, 1096 (2017). doi:10.1038/nchembio.2456 Authors: Huaiying Zhang, Chanat Aonbangkhen, Ekaterina V Tarasovetc, Edward R Ballister, David M Chenoweth & Michael A…

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Kinetochore regulation: Let there be light

Posted on Aug 14th, 2017 - By Ana C Figueiredo

Nature Chemical Biology 13, 1058 (2017). doi:10.1038/nchembio.2464 Authors: Ana C Figueiredo & Helder Maiato Kinetochores form the critical interface with spindle microtubules that accounts for chromosome movement and segregation fidelity during mitosis. Spatial and temporal control of motor protein and checkpoint signaling at kinetochores is now possible with a new set of optogenetic…

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Colibactin assembly line enzymes use S-adenosylmethionine to build a cyclopropane ring

Posted on Aug 7th, 2017 - By Li Zha

Nature Chemical Biology 13, 1063 (2017). doi:10.1038/nchembio.2448 Authors: Li Zha, Yindi Jiang, Matthew T Henke, Matthew R Wilson, Jennifer X Wang, Neil L Kelleher & Emily P Balskus Despite containing an α-amino acid, the versatile cofactor S-adenosylmethionine (SAM) is not a known building block for nonribosomal peptide synthetase (NRPS) assembly lines. Here we report an unusual NRPS module from colibactin biosynthesis that uses SAM for amide bond formation and…

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Bisphosphoglycerate mutase controls serine pathway flux via 3-phosphoglycerate

Posted on Aug 7th, 2017 - By Rob C Oslund

Nature Chemical Biology 13, 1081 (2017). doi:10.1038/nchembio.2453 Authors: Rob C Oslund, Xiaoyang Su, Michael Haugbro, Jung-Min Kee, Mark Esposito, Yael David, Boyuan Wang, Eva Ge, David H Perlman, Yibin Kang, Tom W Muir & Joshua D…

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A genetically encoded tool for manipulation of NADP+/NADPH in living cells

Posted on Aug 7th, 2017 - By Valentin Cracan

Nature Chemical Biology 13, 1088 (2017). doi:10.1038/nchembio.2454 Authors: Valentin Cracan, Denis V Titov, Hongying Shen, Zenon Grabarek & Vamsi K…

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Modulating the DNA polymerase β reaction equilibrium to dissect the reverse reaction

Posted on Jul 31st, 2017 - By David D Shock

Nature Chemical Biology 13, 1074 (2017). doi:10.1038/nchembio.2450 Authors: David D Shock, Bret D Freudenthal, William A Beard & Samuel H…

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Molecular basis for the unusual ring reconstruction in fungal meroterpenoid biogenesis

Posted on Jul 31st, 2017 - By Takahiro Mori

Nature Chemical Biology 13, 1066 (2017). doi:10.1038/nchembio.2443 Authors: Takahiro Mori, Taiki Iwabuchi, Shotaro Hoshino, Hang Wang, Yudai Matsuda & Ikuro…

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Copper import in Escherichia coli by the yersiniabactin metallophore system

Posted on Jul 24th, 2017 - By Eun-Ik Koh

Nature Chemical Biology 13, 1016 (2017). doi:10.1038/nchembio.2441 Authors: Eun-Ik Koh, Anne E Robinson, Nilantha Bandara, Buck E Rogers & Jeffrey P…

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FRET monitoring of a nonribosomal peptide synthetase

Posted on Jul 24th, 2017 - By Jonas Alfermann

Nature Chemical Biology 13, 1009 (2017). doi:10.1038/nchembio.2435 Authors: Jonas Alfermann, Xun Sun, Florian Mayerthaler, Thomas E Morrell, Eva Dehling, Gerrit Volkmann, Tamiki Komatsuzaki, Haw Yang & Henning D…

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Toxicity and repair of DNA adducts produced by the natural product yatakemycin

Posted on Jul 24th, 2017 - By Elwood A Mullins

Nature Chemical Biology 13, 1002 (2017). doi:10.1038/nchembio.2439 Authors: Elwood A Mullins, Rongxin Shi & Brandt F…

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Peptidomimetic inhibitors of APC–Asef interaction block colorectal cancer migration

Posted on Jul 24th, 2017 - By Haiming Jiang

Nature Chemical Biology 13, 994 (2017). doi:10.1038/nchembio.2442 Authors: Haiming Jiang, Rong Deng, Xiuyan Yang, Jialin Shang, Shaoyong Lu, Yanlong Zhao, Kun Song, Xinyi Liu, Qiufen Zhang, Yu Chen, Y Eugene Chinn, Geng Wu, Jian Li, Guoqiang Chen, Jianxiu Yu & Jian…

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Functional annotation of chemical libraries across diverse biological processes

Posted on Jul 24th, 2017 - By Jeff S Piotrowski

Nature Chemical Biology 13, 982 (2017). doi:10.1038/nchembio.2436 Authors: Jeff S Piotrowski, Sheena C Li, Raamesh Deshpande, Scott W Simpkins, Justin Nelson, Yoko Yashiroda, Jacqueline M Barber, Hamid Safizadeh, Erin Wilson, Hiroki Okada, Abraham A Gebre, Karen Kubo, Nikko P Torres, Marissa A LeBlanc, Kerry Andrusiak, Reika Okamoto, Mami Yoshimura, Eva DeRango-Adem, Jolanda van Leeuwen, Katsuhiko Shirahige, Anastasia Baryshnikova, Grant W Brown, Hiroyuki Hirano, Michael…

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Biocatalysis: Achieving aminase activity

Posted on Jul 18th, 2017 - By Caitlin Deane

Nature Chemical Biology 13, 817 (2017). doi:10.1038/nchembio.2447 Author: Caitlin…

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Harnessing yeast organelles for metabolic engineering

Posted on Jul 18th, 2017 - By Sarah K Hammer

Nature Chemical Biology 13, 823 (2017). doi:10.1038/nchembio.2429 Authors: Sarah K Hammer & José L…

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Structural biology: Full monty of family B GPCRs

Posted on Jul 18th, 2017 - By Thue W Schwartz

Nature Chemical Biology 13, 819 (2017). doi:10.1038/nchembio.2438 Authors: Thue W Schwartz & Thomas M Frimurer New structures of the glucagon-like peptide-1 (GLP-1) and glucagon receptors in complex with peptide and nonpeptide ligands provide a comprehensive, detailed picture of the molecular mechanisms of action of family B GPCRs. This opens the door for true structure-based drug discovery aimed at both novel orthosteric and allosteric subsites of the…

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Hints of hidden chemistry

Nature Chemical Biology 13, 815 (2017). doi:10.1038/nchembio.2449 Biosynthetic pathways harbor diverse enzyme functions, and identifying those that catalyze unusual or synthetically challenging transformations offers new routes for biocatalytic…

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Biosynthesis: Methylating mushrooms

Posted on Jul 18th, 2017 - By Albert A Bowers

Nature Chemical Biology 13, 821 (2017). doi:10.1038/nchembio.2437 Author: Albert A Bowers The genome of the poisonous mushroom Omphalotus olearius provides a potent new biocatalytic strategy for installing backbone N-methyl amides on ribosomally synthesized peptides. This discovery could yield new biotechnologies for drug development from peptide…

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Neurodegenerative disease: Not stuck on repeat

Posted on Jul 18th, 2017 - By Mirella Bucci

Nature Chemical Biology 13, 817 (2017). doi:10.1038/nchembio.2444 Author: Mirella…

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Redox regulation: Scaffolding H2O2 signaling

Posted on Jul 18th, 2017 - By Hadley D Sikes

Nature Chemical Biology 13, 818 (2017). doi:10.1038/nchembio.2432 Author: Hadley D Sikes Peroxidases, rather than simply reducing H2O2 to water, also convey oxidation signals to proteins such as transcription factors. A new study reveals how a scaffold protein enables formation of a mixed disulfide between the peroxidase and a transcription…

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Enzymology: Tracking off-targets

Posted on Jul 18th, 2017 - By Alison Farrell

Nature Chemical Biology 13, 817 (2017). doi:10.1038/nchembio.2445 Author: Alison…

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Erratum: The EED protein–protein interaction inhibitor A-395 inactivates the PRC2 complex

Posted on Jul 18th, 2017 - By Yupeng He

Nature Chemical Biology 13, 922 (2017). doi:10.1038/nchembio0817-922b Author: Yupeng He, Sujatha Selvaraju, Michael L Curtin, Clarissa G Jakob, Haizhong Zhu, Kenneth M Comess, Bailin Shaw, Juliana The, Evelyne Lima-Fernandes, Magdalena M Szewczyk, Dong Cheng, Kelly L Klinge, Huan-Qiu Li, Marina Pliushchev, Mikkel A Algire, David Maag, Jun Guo, Justin Dietrich, Sanjay C Panchal, Andrew M Petros, Ramzi F Sweis, Maricel Torrent, Lance J Bigelow, Guillermo Senisterra, Fengling Li,…

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