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  • RNA Splicing: Making the cut
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2018-01-16
    Stéphane Larochelle

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

    更新日期:2018-01-17
  • Plant hormones: Metabolic end run to jasmonate
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2018-01-16
    Gregg A Howe

    Plant hormones: Metabolic end run to jasmonate Plant hormones: Metabolic end run to jasmonate, Published online: 16 January 2018; doi:10.1038/nchembio.2553 The 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 kingdom.

    更新日期:2018-01-17
  • Drug development: Allosteric inhibitors hit USP7 hard
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2018-01-16
    Wei Zhang, Sachdev S Sidhu

    Drug development: Allosteric inhibitors hit USP7 hard Drug development: Allosteric inhibitors hit USP7 hard, Published online: 16 January 2018; doi:10.1038/nchembio.2557 A 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 ligases.

    更新日期:2018-01-17
  • Synthetic biology: License to kill
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2018-01-16
    Caitlin Deane

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

    更新日期:2018-01-17
  • Cell biology: Eaten up from the inside
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2018-01-16
    Karin Kuehnel

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

    更新日期:2018-01-17
  • Errata: Continuous directed evolution of aminoacyl-tRNA synthetases
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2018-01-16
    David I Bryson, Chenguang Fan, Li-Tao Guo, Corwin Miller, Dieter Söll, David R Liu

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

    更新日期:2018-01-17
  • Toward an orthogonal central dogma
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2018-01-16
    Chang C Liu, Michael C Jewett, Jason W Chin, Chris A Voigt

    Toward an orthogonal central dogma Toward an orthogonal central dogma, Published online: 16 January 2018; doi:10.1038/nchembio.2554 The 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 cell.

    更新日期:2018-01-17
  • Natural products: Tapping into personalized chemistry
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2018-01-16
    Jack R Davison, Carole A Bewley

    Natural products: Tapping into personalized chemistry Natural products: Tapping into personalized chemistry, Published online: 16 January 2018; doi:10.1038/nchembio.2560 By 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 drugs.

    更新日期:2018-01-17
  • The molecular basis of subtype selectivity of human kinin G-protein-coupled receptors
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2018-01-15
    Lisa Joedicke, Jiafei Mao, Georg Kuenze, Christoph Reinhart, Tejaswi Kalavacherla, Hendrik R A Jonker, Christian Richter, Harald Schwalbe, Jens Meiler, Julia Preu, Hartmut Michel, Clemens Glaubitz

    G-protein-coupled receptors (GPCRs) are the most important signal transducers in higher eukaryotes. Despite considerable progress, the molecular basis of subtype-specific ligand selectivity, especially for peptide receptors, remains unknown. Here, by integrating DNP-enhanced solid-state NMR spectroscopy with advanced molecular modeling and docking, the mechanism of the subtype selectivity of human bradykinin receptors for their peptide agonists has been resolved. The conserved middle segments of the bound peptides show distinct conformations that result in different presentations of their N and C termini toward their receptors. Analysis of the peptide–receptor interfaces reveals that the charged N-terminal residues of the peptides are mainly selected through electrostatic interactions, whereas the C-terminal segments are recognized via both conformations and interactions. The detailed molecular picture obtained by this approach opens a new gateway for exploring the complex conformational and chemical space of peptides and peptide analogs for designing GPCR subtype-selective biochemical tools and drugs.

    更新日期:2018-01-15
  • A de novo enzyme catalyzes a life-sustaining reaction in Escherichia coli
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2018-01-15
    Ann E Donnelly, Grant S Murphy, Katherine M Digianantonio, Michael H Hecht

    Producing novel enzymes that are catalytically active in vitro and biologically functional in vivo is a key goal of synthetic biology. Here we describe Syn-F4, the first de novo protein that meets both criteria. Purified Syn-F4 hydrolyzes the siderophore ferric enterobactin, and expression of Syn-F4 allows an inviable strain of Escherichia coli to grow in iron-limited medium. These findings demonstrate that entirely new sequences can provide life-sustaining enzymatic functions in living organisms.

    更新日期:2018-01-15
  • Light-activated chemical probing of nucleobase solvent accessibility inside cells
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2018-01-15
    Chao Feng, Dalen Chan, Jojo Joseph, Mikko Muuronen, William H Coldren, Nan Dai, Ivan R Corrêa Jr, Filipp Furche, Christopher M Hadad, Robert C Spitale

    The discovery of functional RNAs that are critical for normal and disease physiology continues to expand at a breakneck pace. Many RNA functions are controlled by the formation of specific structures, and an understanding of each structural component is necessary to elucidate its function. Measuring solvent accessibility intracellularly with experimental ease is an unmet need in the field. Here, we present a novel method for probing nucleobase solvent accessibility, Light Activated Structural Examination of RNA (LASER). LASER depends on light activation of a small molecule, nicotinoyl azide (NAz), to measure solvent accessibility of purine nucleobases. In vitro, this technique accurately monitors solvent accessibility and identifies rapid structural changes resulting from ligand binding in a metabolite-responsive RNA. LASER probing can further identify cellular RNA–protein interactions and unique intracellular RNA structures. Our photoactivation technique provides an adaptable framework to structurally characterize solvent accessibility of RNA in many environments.

    更新日期:2018-01-15
  • Na+-mimicking ligands stabilize the inactive state of leukotriene B4 receptor BLT1
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2018-01-08
    Tetsuya Hori, Toshiaki Okuno, Kunio Hirata, Keitaro Yamashita, Yoshiaki Kawano, Masaki Yamamoto, Masakatsu Hato, Motonao Nakamura, Takao Shimizu, Takehiko Yokomizo, Masashi Miyano, Shigeyuki Yokoyama

    Most G-protein-coupled receptors (GPCRs) are stabilized in common in the inactive state by the formation of the sodium ion–centered water cluster with the conserved Asp2.50 inside the seven-transmembrane domain. We determined the crystal structure of the leukotriene B4 (LTB4) receptor BLT1 bound with BIIL260, a chemical bearing a benzamidine moiety. Surprisingly, the amidine group occupies the sodium ion and water locations, interacts with D662.50, and mimics the entire sodium ion–centered water cluster. Thus, BLT1 is fixed in the inactive state, and the transmembrane helices cannot change their conformations to form the active state. Moreover, the benzamidine molecule alone serves as a negative allosteric modulator for BLT1. As the residues involved in the benzamidine binding are widely conserved among GPCRs, the unprecedented inverse-agonist mechanism by the benzamidine moiety could be adapted to other GPCRs. Consequently, the present structure will enable the rational development of inverse agonists specific for each GPCR.

    更新日期:2018-01-08
  • Mechanism of intersubunit ketosynthase–dehydratase interaction in polyketide synthases
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2018-01-08
    Matthew Jenner, Simone Kosol, Daniel Griffiths, Panward Prasongpholchai, Lucio Manzi, Andrew S Barrow, John E Moses, Neil J Oldham, Józef R Lewandowski, Gregory L Challis

    Modular polyketide synthases (PKSs) produce numerous structurally complex natural products that have diverse applications in medicine and agriculture. PKSs typically consist of several multienzyme subunits that utilize structurally defined docking domains (DDs) at their N and C termini to ensure correct assembly into functional multiprotein complexes. Here we report a fundamentally different mechanism for subunit assembly in trans-acyltransferase (trans-AT) modular PKSs at the junction between ketosynthase (KS) and dehydratase (DH) domains. This mechanism involves direct interaction of a largely unstructured docking domain (DD) at the C terminus of the KS with the surface of the downstream DH. Acyl transfer assays and mechanism-based crosslinking established that the DD is required for the KS to communicate with the acyl carrier protein appended to the DH. Two distinct regions for binding of the DD to the DH were identified using NMR spectroscopy, carbene footprinting, and mutagenesis, providing a foundation for future elucidation of the molecular basis for interaction specificity.

    更新日期:2018-01-08
  • Employing a biochemical protecting group for a sustainable indigo dyeing strategy
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2018-01-08
    Tammy M Hsu, Ditte H Welner, Zachary N Russ, Bernardo Cervantes, Ramya L Prathuri, Paul D Adams, John E Dueber

    Indigo is an ancient dye uniquely capable of producing the signature tones in blue denim; however, the dyeing process requires chemical steps that are environmentally damaging. We describe a sustainable dyeing strategy that not only circumvents the use of toxic reagents for indigo chemical synthesis but also removes the need for a reducing agent for dye solubilization. This strategy utilizes a glucose moiety as a biochemical protecting group to stabilize the reactive indigo precursor indoxyl to form indican, preventing spontaneous oxidation to crystalline indigo during microbial fermentation. Application of a β-glucosidase removes the protecting group from indican, resulting in indigo crystal formation in the cotton fibers. We identified the gene coding for the glucosyltransferase PtUGT1 from the indigo plant Polygonum tinctorium and solved the structure of PtUGT1. Heterologous expression of PtUGT1 in Escherichia coli supported high indican conversion, and biosynthesized indican was used to dye cotton swatches and a garment.

    更新日期:2018-01-08
  • Accessing chemical diversity from the uncultivated symbionts of small marine animals
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2018-01-01
    Thomas E Smith, Christopher D Pond, Elizabeth Pierce, Zachary P Harmer, Jason Kwan, Malcolm M Zachariah, Mary Kay Harper, Thomas P Wyche, Teatulohi K Matainaho, Tim S Bugni, Louis R Barrows, Chris M Ireland, Eric W Schmidt

    Chemistry drives many biological interactions between the microbiota and host animals, yet it is often challenging to identify the chemicals involved. This poses a problem, as such small molecules are excellent sources of potential pharmaceuticals, pretested by nature for animal compatibility. We discovered anti-HIV compounds from small, marine tunicates from the Eastern Fields of Papua New Guinea. Tunicates are a reservoir for new bioactive chemicals, yet their small size often impedes identification or even detection of the chemicals within. We solved this problem by combining chemistry, metagenomics, and synthetic biology to directly identify and synthesize the natural products. We show that these anti-HIV compounds, the divamides, are a novel family of lanthipeptides produced by symbiotic bacteria living in the tunicate. Neighboring animal colonies contain structurally related divamides that differ starkly in their biological properties, suggesting a role for biosynthetic plasticity in a native context wherein biological interactions take place.

    更新日期:2018-01-01
  • An OPR3-independent pathway uses 4,5-didehydrojasmonate for jasmonate synthesis
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2018-01-01
    Andrea Chini, Isabel Monte, Angel M Zamarreño, Mats Hamberg, Steve Lassueur, Philippe Reymond, Sally Weiss, Annick Stintzi, Andreas Schaller, Andrea Porzel, José M García-Mina, Roberto Solano

    Biosynthesis of the phytohormone jasmonoyl-isoleucine (JA-Ile) requires reduction of the JA precursor 12-oxo-phytodienoic acid (OPDA) by OPDA reductase 3 (OPR3). Previous analyses of the opr3-1 Arabidopsis mutant suggested an OPDA signaling role independent of JA-Ile and its receptor COI1; however, this hypothesis has been challenged because opr3-1 is a conditional allele not completely impaired in JA-Ile biosynthesis. To clarify the role of OPR3 and OPDA in JA-independent defenses, we isolated and characterized a loss-of-function opr3-3 allele. Strikingly, opr3-3 plants remained resistant to necrotrophic pathogens and insect feeding, and activated COI1-dependent JA-mediated gene expression. Analysis of OPDA derivatives identified 4,5-didehydro-JA in wounded wild-type and opr3-3 plants. OPR2 was found to reduce 4,5-didehydro-JA to JA, explaining the accumulation of JA-Ile and activation of JA-Ile-responses in opr3-3 mutants. Our results demonstrate that in the absence of OPR3, OPDA enters the β-oxidation pathway to produce 4,5-ddh-JA as a direct precursor of JA and JA-Ile, thus identifying an OPR3-independent pathway for JA biosynthesis.

    更新日期:2018-01-01
  • Expression system for structural and functional studies of human glycosylation enzymes
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-12-18
    Kelley W Moremen, Annapoorani Ramiah, Melissa Stuart, Jason Steel, Lu Meng, Farhad Forouhar, Heather A Moniz, Gagandeep Gahlay, Zhongwei Gao, Digantkumar Chapla, Shuo Wang, Jeong-Yeh Yang, Pradeep Kumar Prabhakar, Roy Johnson, Mitche dela Rosa, Christoph Geisler, Alison V Nairn, Jayaraman Seetharaman, Sheng-Cheng Wu, Liang Tong, Harry J Gilbert, Joshua LaBaer, Donald L Jarvis

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

    更新日期:2017-12-18
  • A role for 2-Cys peroxiredoxins in facilitating cytosolic protein thiol oxidation
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-12-18
    Sarah Stöcker, Michael Maurer, Thomas Ruppert, Tobias P Dick

    A role for 2-Cys peroxiredoxins in facilitating cytosolic protein thiol oxidation A role for 2-Cys peroxiredoxins in facilitating cytosolic protein thiol oxidation, Published online: 18 December 2017; doi:10.1038/nchembio.2536 Cytosolic 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 signals.

    更新日期:2017-12-18
  • Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-12-18
    Calla M Olson, Baishan Jiang, Michael A Erb, Yanke Liang, Zainab M Doctor, Zinan Zhang, Tinghu Zhang, Nicholas Kwiatkowski, Myriam Boukhali, Jennifer L Green, Wilhelm Haas, Tyzoon Nomanbhoy, Eric S Fischer, Richard A Young, James E Bradner, Georg E Winter, Nathanael S Gray

    Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation, Published online: 18 December 2017; doi:10.1038/nchembio.2538 A 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 compared.

    更新日期:2017-12-18
  • RNA modifications: Ribosomes get decorated
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-12-12
    Mirella Bucci

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

    更新日期:2017-12-13
  • Notch signaling: A sweet strategy
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-12-12
    Tetsuya Okajima

    Notch signaling: A sweet strategy Notch signaling: A sweet strategy, Published online: 12 December 2017; doi:10.1038/nchembio.2532 Glycosylation 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 interactions.

    更新日期:2017-12-13
  • Resistance mechanisms: Watering down a warhead
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-12-12
    Caitlin Deane

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

    更新日期:2017-12-13
  • Neurobiology: Defining your territory
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-12-12
    Grant Miura

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

    更新日期:2017-12-13
  • Protein engineering: Finding the best ligase
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-12-12
    Christian F W Becker

    Protein engineering: Finding the best ligase Protein engineering: Finding the best ligase, Published online: 12 December 2017; doi:10.1038/nchembio.2533 Modification 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 engineering.

    更新日期:2017-12-13
  • Microbiology: Trapping Rac1
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-12-12
    Karin Kuehnel

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

    更新日期:2017-12-13
  • Structure-inspired design of β-arrestin-biased ligands for aminergic GPCRs
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-12-11
    John D McCorvy, Kyle V Butler, Brendan Kelly, Katie Rechsteiner, Joel Karpiak, Robin M Betz, Bethany L Kormos, Brian K Shoichet, Ron O Dror, Jian Jin, Bryan L Roth

    Structure-inspired design of β-arrestin-biased ligands for aminergic GPCRs Structure-inspired design of β-arrestin-biased ligands for aminergic GPCRs, Published online: 11 December 2017; doi:10.1038/nchembio.2527 Development 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 signaling.

    更新日期:2017-12-11
  • Engineered synthetic scaffolds for organizing proteins within the bacterial cytoplasm
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-12-11
    Matthew J Lee, Judith Mantell, Lorna Hodgson, Dominic Alibhai, Jordan M Fletcher, Ian R Brown, Stefanie Frank, Wei-Feng Xue, Paul Verkade, Derek N Woolfson, Martin J Warren

    Engineered synthetic scaffolds for organizing proteins within the bacterial cytoplasm Engineered synthetic scaffolds for organizing proteins within the bacterial cytoplasm, Published online: 11 December 2017; doi:10.1038/nchembio.2535 Two 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 flux.

    更新日期:2017-12-11
  • Inhibiting mitochondrial phosphate transport as an unexploited antifungal strategy
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-12-11
    Catherine A McLellan, Benjamin M Vincent, Norma V Solis, Alex K Lancaster, Lucas B Sullivan, Cathy L Hartland, Willmen Youngsaye, Scott G Filler, Luke Whitesell, Susan Lindquist

    Inhibiting mitochondrial phosphate transport as an unexploited antifungal strategy Inhibiting mitochondrial phosphate transport as an unexploited antifungal strategy, Published online: 11 December 2017; doi:10.1038/nchembio.2534 A potent inhibitor of the conditionally essential mitochondrial phosphate carrier protein Mir1 in the fungi Candida albicans diminishes mitochondrial oxygen consumption and causes dramatic changes in concentrations of citrate and succinate.

    更新日期:2017-12-11
  • Human antibody-based chemically induced dimerizers for cell therapeutic applications
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-12-04
    Zachary B Hill, Alexander J Martinko, Duy P Nguyen, James A Wells

    Human antibody-based chemically induced dimerizers for cell therapeutic applications Human antibody-based chemically induced dimerizers for cell therapeutic applications, Published online: 04 December 2017; doi:10.1038/nchembio.2529 Selections 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 therapies.

    更新日期:2017-12-05
  • Discovery and characterization of highly potent and selective allosteric USP7 inhibitors
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-12-04
    Gerald Gavory, Colin R O'Dowd, Matthew D Helm, Jakub Flasz, Elias Arkoudis, Anthony Dossang, Caroline Hughes, Eamon Cassidy, Keeva McClelland, Ewa Odrzywol, Natalie Page, Oliver Barker, Hugues Miel, Timothy Harrison

    Discovery and characterization of highly potent and selective allosteric USP7 inhibitors Discovery and characterization of highly potent and selective allosteric USP7 inhibitors, Published online: 04 December 2017; doi:10.1038/nchembio.2528 A 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 compound.

    更新日期:2017-12-05
  • 5-Formylcytosine to cytosine conversion by C–C bond cleavage in vivo
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-27
    Katharina Iwan, René Rahimoff, Angie Kirchner, Fabio Spada, Arne S Schröder, Olesea Kosmatchev, Shqiponja Ferizaj, Jessica Steinbacher, Edris Parsa, Markus Müller, Thomas Carell

    5-Formylcytosine to cytosine conversion by C–C bond cleavage in vivo 5-Formylcytosine to cytosine conversion by C–C bond cleavage in vivo, Published online: 27 November 2017; doi:10.1038/nchembio.2531 Direct 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 cells.

    更新日期:2017-11-28
  • Inhibition of Delta-induced Notch signaling using fucose analogs
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-27
    Michael Schneider, Vivek Kumar, Lars Ulrik Nordstrøm, Lei Feng, Hideyuki Takeuchi, Huilin Hao, Vincent C Luca, K Christopher Garcia, Pamela Stanley, Peng Wu, Robert S Haltiwanger

    Inhibition of Delta-induced Notch signaling using fucose analogs Inhibition of Delta-induced Notch signaling using fucose analogs, Published online: 27 November 2017; doi:10.1038/nchembio.2520 Protein 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 signaling.

    更新日期:2017-11-28
  • 5-Formylcytosine to cytosine conversion by C–C bond cleavage in vivo
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-27
    Katharina Iwan, René Rahimoff, Angie Kirchner, Fabio Spada, Arne S Schröder, Olesea Kosmatchev, Shqiponja Ferizaj, Jessica Steinbacher, Edris Parsa, Markus Müller, Thomas Carell

    5-Formylcytosine to cytosine conversion by C–C bond cleavage in vivo 5-Formylcytosine to cytosine conversion by C–C bond cleavage in vivo, Published online: 27 November 2017; doi:10.1038/nchembio.2531 Direct 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 cells.

    更新日期:2017-11-28
  • Inhibition of Delta-induced Notch signaling using fucose analogs
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-27
    Michael Schneider, Vivek Kumar, Lars Ulrik Nordstrøm, Lei Feng, Hideyuki Takeuchi, Huilin Hao, Vincent C Luca, K Christopher Garcia, Pamela Stanley, Peng Wu, Robert S Haltiwanger

    Inhibition of Delta-induced Notch signaling using fucose analogs Inhibition of Delta-induced Notch signaling using fucose analogs, Published online: 27 November 2017; doi:10.1038/nchembio.2520 Protein 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 signaling.

    更新日期:2017-11-28
  • Genetic code expansion: Synthetases pick up the PACE
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-21
    Jeffery M Tharp, Wenshe R Liu

    Genetic code expansion: Synthetases pick up the PACE Genetic code expansion: Synthetases pick up the PACE, Published online: 21 November 2017; doi:10.1038/nchembio.2516 Phage-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 orthogonality.

    更新日期:2017-11-22
  • Errata: Functional annotation of chemical libraries across diverse biological processes
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-21
    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 Costanzo, Brenda Andrews, Yoshikazu Ohya, Hiroyuki Osada, Minoru Yoshida, Chad L Myers, Charles Boone

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

    更新日期:2017-11-22
  • Nucleic acids: mRNAs get a TREAT
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-21
    Grant Miura

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

    更新日期:2017-11-22
  • Host–pathogen interactions: A ubiquitin defense
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-21
    Mirella Bucci

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

    更新日期:2017-11-22
  • Errata: Functional annotation of chemical libraries across diverse biological processes
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-21
    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 Costanzo, Brenda Andrews, Yoshikazu Ohya, Hiroyuki Osada, Minoru Yoshida, Chad L Myers, Charles Boone

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

    更新日期:2017-11-22
  • Cancer systems biology: Harnessing off-target effects
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-21
    Gaye Saginc, Franziska Voellmy, Rune Linding

    Cancer systems biology: Harnessing off-target effects Cancer systems biology: Harnessing off-target effects, Published online: 21 November 2017; doi:10.1038/nchembio.2519 The '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 action.

    更新日期:2017-11-22
  • Peptide design: Hacking hemagglutinin
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-21
    Karin Kuehnel

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

    更新日期:2017-11-22
  • Enzymology: I want my cluster back
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-21
    Caitlin Deane

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

    更新日期:2017-11-22
  • Genetic code expansion: Synthetases pick up the PACE
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-21
    Jeffery M Tharp, Wenshe R Liu

    Genetic code expansion: Synthetases pick up the PACE Genetic code expansion: Synthetases pick up the PACE, Published online: 21 November 2017; doi:10.1038/nchembio.2516 Phage-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 orthogonality.

    更新日期:2017-11-22
  • Errata: Functional annotation of chemical libraries across diverse biological processes
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-21
    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 Costanzo, Brenda Andrews, Yoshikazu Ohya, Hiroyuki Osada, Minoru Yoshida, Chad L Myers, Charles Boone

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

    更新日期:2017-11-22
  • Nucleic acids: mRNAs get a TREAT
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-21
    Grant Miura

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

    更新日期:2017-11-22
  • Host–pathogen interactions: A ubiquitin defense
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-21
    Mirella Bucci

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

    更新日期:2017-11-22
  • Errata: Functional annotation of chemical libraries across diverse biological processes
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-21
    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 Costanzo, Brenda Andrews, Yoshikazu Ohya, Hiroyuki Osada, Minoru Yoshida, Chad L Myers, Charles Boone

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

    更新日期:2017-11-22
  • Cancer systems biology: Harnessing off-target effects
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-21
    Gaye Saginc, Franziska Voellmy, Rune Linding

    Cancer systems biology: Harnessing off-target effects Cancer systems biology: Harnessing off-target effects, Published online: 21 November 2017; doi:10.1038/nchembio.2519 The '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 action.

    更新日期:2017-11-22
  • Peptide design: Hacking hemagglutinin
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-21
    Karin Kuehnel

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

    更新日期:2017-11-22
  • Enzymology: I want my cluster back
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-21
    Caitlin Deane

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

    更新日期:2017-11-22
  • Small-molecule inhibition of TLR8 through stabilization of its resting state
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-20
    Shuting Zhang, Zhenyi Hu, Hiromi Tanji, Shuangshuang Jiang, Nabanita Das, Jing Li, Kentaro Sakaniwa, Jin Jin, Yanyan Bian, Umeharu Ohto, Toshiyuki Shimizu, Hang Yin

    Small-molecule inhibition of TLR8 through stabilization of its resting state Small-molecule inhibition of TLR8 through stabilization of its resting state, Published online: 20 November 2017; doi:10.1038/nchembio.2518 High-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 interface.

    更新日期:2017-11-21
  • Monobactam formation in sulfazecin by a nonribosomal peptide synthetase thioesterase
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-20
    Ryan A Oliver, Rongfeng Li, Craig A Townsend

    Monobactam formation in sulfazecin by a nonribosomal peptide synthetase thioesterase Monobactam formation in sulfazecin by a nonribosomal peptide synthetase thioesterase, Published online: 20 November 2017; doi:10.1038/nchembio.2526 Biosynthesis 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 moiety.

    更新日期:2017-11-21
  • Engineering peptide ligase specificity by proteomic identification of ligation sites
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-20
    Amy M Weeks, James A Wells

    Engineering peptide ligase specificity by proteomic identification of ligation sites Engineering peptide ligase specificity by proteomic identification of ligation sites, Published online: 20 November 2017; doi:10.1038/nchembio.2521 A 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 terminome.

    更新日期:2017-11-21
  • Small-molecule inhibition of TLR8 through stabilization of its resting state
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-20
    Shuting Zhang, Zhenyi Hu, Hiromi Tanji, Shuangshuang Jiang, Nabanita Das, Jing Li, Kentaro Sakaniwa, Jin Jin, Yanyan Bian, Umeharu Ohto, Toshiyuki Shimizu, Hang Yin

    Small-molecule inhibition of TLR8 through stabilization of its resting state Small-molecule inhibition of TLR8 through stabilization of its resting state, Published online: 20 November 2017; doi:10.1038/nchembio.2518 High-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 interface.

    更新日期:2017-11-21
  • Monobactam formation in sulfazecin by a nonribosomal peptide synthetase thioesterase
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-20
    Ryan A Oliver, Rongfeng Li, Craig A Townsend

    Monobactam formation in sulfazecin by a nonribosomal peptide synthetase thioesterase Monobactam formation in sulfazecin by a nonribosomal peptide synthetase thioesterase, Published online: 20 November 2017; doi:10.1038/nchembio.2526 Biosynthesis 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 moiety.

    更新日期:2017-11-21
  • Engineering peptide ligase specificity by proteomic identification of ligation sites
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-20
    Amy M Weeks, James A Wells

    Engineering peptide ligase specificity by proteomic identification of ligation sites Engineering peptide ligase specificity by proteomic identification of ligation sites, Published online: 20 November 2017; doi:10.1038/nchembio.2521 A 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 terminome.

    更新日期:2017-11-21
  • Synthetic microbial consortia enable rapid assembly of pure translation machinery
    Nat. Chem. Biol. (IF 15.066) Pub Date : 
    Fernando Villarreal, Luis E Contreras-Llano, Michael Chavez, Yunfeng Ding, Jinzhen Fan, Tingrui Pan, Cheemeng Tan

    Synthetic microbial consortia enable rapid assembly of pure translation machinery Synthetic microbial consortia enable rapid assembly of pure translation machinery, Published online: 13 November 2017; doi:10.1038/nchembio.2514 NatureArticleSnippet(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, and purification procedure. , isJats=true)

    更新日期:2017-11-13
  • Nonimmune cells equipped with T-cell-receptor-like signaling for cancer cell ablation
    Nat. Chem. Biol. (IF 15.066) Pub Date : 
    Ryosuke Kojima, Leo Scheller, Martin Fussenegger

    Nonimmune cells equipped with T-cell-receptor-like signaling for cancer cell ablation Nonimmune cells equipped with T-cell-receptor-like signaling for cancer cell ablation, Published online: 13 November 2017; doi:10.1038/nchembio.2498 NatureArticleSnippet(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 an alternative strategy to chimeric antigen receptor T-cell (CAR-T) technology. , isJats=true)

    更新日期:2017-11-13
  • Top-down characterization of endogenous protein complexes with native proteomics
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-13
    Owen S Skinner, Nicole A Haverland, Luca Fornelli, Rafael D Melani, Luis H F Do Vale, Henrique S Seckler, Peter F Doubleday, Luis F Schachner, Kristina Srzentić, Neil L Kelleher, Philip D Compton

    Top-down characterization of endogenous protein complexes with native proteomics Top-down characterization of endogenous protein complexes with native proteomics, Published online: 13 November 2017; doi:10.1038/nchembio.2515 NatureArticleSnippet(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 cofactors and ligands. , isJats=true)

    更新日期:2017-11-13
  • Metabolomics-based discovery of a metabolite that enhances oligodendrocyte maturation
    Nat. Chem. Biol. (IF 15.066) Pub Date : 2017-11-13
    Brittney A Beyer, Mingliang Fang, Benjamin Sadrian, J Rafael Montenegro-Burke, Warren C Plaisted, Bernard P C Kok, Enrique Saez, Toru Kondo, Gary Siuzdak, Luke L Lairson

    Metabolomics-based discovery of a metabolite that enhances oligodendrocyte maturation Metabolomics-based discovery of a metabolite that enhances oligodendrocyte maturation, Published online: 13 November 2017; doi:10.1038/nchembio.2517 NatureArticleSnippet(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. , isJats=true)

    更新日期:2017-11-13
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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