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Nature Chemical Biology Contents: January 2018, Volume 14 No 1 pp 1 - 101

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Nature Chemical Biology

TABLE OF CONTENTS

January 2018 Volume 14, Issue 1

Research Highlights
News and Views
Brief Communication
Articles

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Nature Research present this Collection of articles celebrating the 2017 Nobel Prize in Chemistry to Jacques Dubochet, Joachim Frank and Richard Henderson, recognised "for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution".
 
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Research Highlights

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Microbiology: Trapping Rac1 | Resistance mechanisms: Watering down a warhead | RNA modifications: Ribosomes get decorated | Neurobiology: Defining your territory


News and Views

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Protein engineering: Finding the best ligase   pp2 - 3
Christian F W Becker
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.

See also: Article by Weeks & Wells

Notch signaling: A sweet strategy   pp3 - 4
Tetsuya Okajima
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.

See also: Article by Schneider et al.

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Brief Communication

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Monobactam formation in sulfazecin by a nonribosomal peptide synthetase thioesterase   pp5 - 7
Ryan A Oliver, Rongfeng Li and Craig A Townsend
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.
Chemical compounds

Articles

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Purinyl-cobamide is a native prosthetic group of reductive dehalogenases   pp8 - 14
Jun Yan, Meng Bi, Allen K Bourdon, Abigail T Farmer, Po-Hsiang Wang et al.
doi:10.1038/nchembio.2512



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 function.
Chemical compounds

Ultrasensitive optical imaging with lanthanide lumiphores   pp15 - 21
Ukrae Cho, Daniel P Riordan, Paulina Ciepla, Kiranmai S Kocherlakota, James K Chen et al.
doi:10.1038/nchembio.2513



Ultrasensitive imaging of lanthanide chelates is achieved by integrating transreflected illumination, luminescence resonance energy transfer, and time-resolved microscopy.

Metabolomics-based discovery of a metabolite that enhances oligodendrocyte maturation   pp22 - 28
Brittney A Beyer, Mingliang Fang, Benjamin Sadrian, J Rafael Montenegro-Burke, Warren C Plaisted et al.
doi:10.1038/nchembio.2517



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.

Synthetic microbial consortia enable rapid assembly of pure translation machinery   pp29 - 35
Fernando Villarreal, Luis E Contreras-Llano, Michael Chavez, Yunfeng Ding, Jinzhen Fan et al.
doi:10.1038/nchembio.2514



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.

Top-down characterization of endogenous protein complexes with native proteomics   pp36 - 41
Owen S Skinner, Nicole A Haverland, Luca Fornelli, Rafael D Melani, Luis H F Do Vale et al.
doi:10.1038/nchembio.2515



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.

Nonimmune cells equipped with T-cell-receptor-like signaling for cancer cell ablation   pp42 - 49
Ryosuke Kojima, Leo Scheller and Martin Fussenegger
doi:10.1038/nchembio.2498



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.

Engineering peptide ligase specificity by proteomic identification of ligation sites   pp50 - 57
Amy M Weeks and James A Wells
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.
Chemical compounds
See also: News and Views by Becker

Small-molecule inhibition of TLR8 through stabilization of its resting state   pp58 - 64
Shuting Zhang, Zhenyi Hu, Hiromi Tanji, Shuangshuang Jiang, Nabanita Das et al.
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.
Chemical compounds

Inhibition of Delta-induced Notch signaling using fucose analogs   pp65 - 71
Michael Schneider, Vivek Kumar, Lars Ulrik Nordstrom, Lei Feng, Hideyuki Takeuchi et al.
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.
Chemical compounds
See also: News and Views by Okajima

5-Formylcytosine to cytosine conversion by C-C bond cleavage in vivo   pp72 - 78
Katharina Iwan, Rene Rahimoff, Angie Kirchner, Fabio Spada, Arne S Schroder et al.
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.
Chemical compounds

PatB1 is an O-acetyltransferase that decorates secondary cell wall polysaccharides   pp79 - 85
David Sychantha, Dustin J Little, Robert N Chapman, Geert-Jan Boons, Howard Robinson et al.
doi:10.1038/nchembio.2509



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 insights into its catalytic mechanism.
Chemical compounds

Synthetic beta cells for fusion-mediated dynamic insulin secretion   pp86 - 93
Zhaowei Chen, Jinqiang Wang, Wujin Sun, Edikan Archibong, Anna R Kahkoska et al.
doi:10.1038/nchembio.2511



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.

Small molecule promotes β-catenin citrullination and inhibits Wnt signaling in cancer   pp94 - 101
Yi Qu, Jan Roger Olsen, Xing Yuan, Phil F Cheng, Mitchell P Levesque et al.
doi:10.1038/nchembio.2510



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 results in proteasomal degradation.
Chemical compounds

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