Nature Chemical Biology

Shaping embryonic development ()
The growing intersection between chemical tools and principles and developmental biology is providing new insights into the molecular-level details of developmental processes.
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Small-molecule phenotypic screening with stem cells ()
To fully leverage the potential of human-induced pluripotent stem cells (hiPSCs), improved and standardized reprogramming methods and large-scale collections of hiPSC lines are needed, and the stem cell community must embrace chemical biology methodology for target identification and validation.
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Unraveling cell-to-cell signaling networks with chemical biology ()
Cell-to-cell signaling networks, although poorly understood, guide tissue development, regulate tissue function and may become dysregulated in disease. Chemical biologists can develop the next generation of tools to untangle these complex and dynamic networks of interacting cells.
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Synthetic biology: Return to sender ()

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Enzymology: Radical ring resizing ()

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Infectious disease: A lethal sugar fix ()

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Plant development: Get lit on steroids ()

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Signal Transduction: Notch catches a Jagged edge ()
Notch signaling is an essential cell–cell communication pathway that influences numerous cell fate decisions during development. Structural and biochemical studies of a Notch–Jagged complex dramatically advance current understanding of ligand recognition, and reveal evidence of catch-bond behavior in the complex.
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Immunology: Mind the immuno-connection gap ()
Biologic drugs that modulate the immune system have revolutionized the therapeutic landscape for several selected cancer types. A new study reports an image-based assay system to monitor cell–cell interactions, identifying small-molecule compounds with immunomodulatory capacity.
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Optogenetics: Switching with red and blue ()
Multiple optogenetic technologies are required to control biological activity simultaneously with different colors of light. Optimizing a near-infrared-induced heterodimerization system, which can be combined with blue-light-controlled domains, enables precise spatiotemporal control of target molecules in live mammalian cells.
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Protein degradation: DCAFinating splicing ()
Chemical control of protein homeostasis and induction of protein destabilization are emerging therapeutic strategies. Two recent studies identify a set of sulfonamides that can modulate the CRL4DCAF15 E3 ligase complex to target the splicing factor RBM39 for proteasomal degradation.
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Small-molecule pheromones and hormones controlling nematode development ()

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Illuminating developmental biology through photochemistry ()

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The perception of strigolactones in vascular plants ()

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CRISPR–Cas9 strategy for activation of silent Streptomyces biosynthetic gene clusters ()
Here we report an efficient CRISPR–Cas9 knock-in strategy to activate silent biosynthetic gene clusters (BGCs) in streptomycetes. We applied this one-step strategy to activate multiple BGCs of different classes in five Streptomyces species and triggered the production of unique metabolites, including a novel pentangular type II polyketide in Streptomyces viridochromogenes. This potentially scalable strategy complements existing activation approaches and facilitates discovery efforts to uncover new compounds with interesting bioactivities.
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Structural and functional insight into human O-GlcNAcase ()
O-GlcNAc hydrolase (OGA) removes O-linked N-acetylglucosamine (O-GlcNAc) from a myriad of nucleocytoplasmic proteins. Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value.
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Insights into activity and inhibition from the crystal structure of human O-GlcNAcase ()
O-GlcNAc hydrolase (OGA) catalyzes removal of βα-linked N-acetyl-D-glucosamine from serine and threonine residues. We report crystal structures of Homo sapiens OGA catalytic domain in apo and inhibited states, revealing a flexible dimer that displays three unique conformations and is characterized by subdomain α-helix swapping. These results identify new structural features of the substrate-binding groove adjacent to the catalytic site and open new opportunities for structural, mechanistic and drug discovery activities.
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Chemical screening identifies ATM as a target for alleviating senescence ()

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Diabetes reversal by inhibition of the low-molecular-weight tyrosine phosphatase ()

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Near-infrared optogenetic pair for protein regulation and spectral multiplexing ()

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AtaT blocks translation initiation by N-acetylation of the initiator tRNAfMet ()

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Phosphorylated glycosphingolipids essential for cholesterol mobilization in Caenorhabditis elegans ()

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Mechanistic insights into energy conservation by flavin-based electron bifurcation ()

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Using the pimeloyl-CoA synthetase adenylation fold to synthesize fatty acid thioesters ()

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The pimeloyl-CoA synthetase BioW defines a new fold for adenylate-forming enzymes ()

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Selective degradation of splicing factor CAPERα by anticancer sulfonamides ()

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Global survey of the immunomodulatory potential of common drugs ()

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

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Erratum: Full antagonism of the estrogen receptor without a prototypical ligand side chain ()

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Corrigendum: Full antagonism of the estrogen receptor without a prototypical ligand side chain ()

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