Journal: Nature Chemical Biology

Abbreviation

Nat Chem Biol

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Nature

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ISSN

1552-4450
1552-4469

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Publications 1 - 10 of 65
  • Encoding chemistry
    Item type: Journal Article
    Neri, Dario; Brändli, André W. (2009)
    Nature Chemical Biology
  • Structures and function of the amino acid polymerase cyanophycin synthetase
    Item type: Journal Article
    Sharon, Itai; Haque, Asfarul S.; Grogg, Marcel; et al. (2021)
    Nature Chemical Biology
    Cyanophycin is a natural biopolymer produced by a wide range of bacteria, consisting of a chain of poly-l-Asp residues with l-Arg residues attached to the beta-carboxylate sidechains by isopeptide bonds. Cyanophycin is synthesized from ATP, aspartic acid and arginine by a homooligomeric enzyme called cyanophycin synthetase (CphA1). CphA1 has domains that are homologous to glutathione synthetases and muramyl ligases, but no other structural information has been available. Here, we present cryo-electron microscopy and X-ray crystallography structures of cyanophycin synthetases from three different bacteria, including cocomplex structures of CphA1 with ATP and cyanophycin polymer analogs at 2.6 angstrom resolution. These structures reveal two distinct tetrameric architectures, show the configuration of active sites and polymer-binding regions, indicate dynamic conformational changes and afford insight into catalytic mechanism. Accompanying biochemical interrogation of substrate binding sites, catalytic centers and oligomerization interfaces combine with the structures to provide a holistic understanding of cyanophycin biosynthesis.
  • Designed cell consortia as fragrance-programmable analog-to-digital converters
    Item type: Journal Article
    Müller, Marius; Ausländer, Simon; Spinnler, Andrea; et al. (2017)
    Nature Chemical Biology
  • A solid beta-sheet structure is formed at the surface of FUS droplets during aging
    Item type: Journal Article
    Emmanouilidis, Leonidas; Bartalucci, Ettore; Kan, Yelena; et al. (2024)
    Nature Chemical Biology
    Phase transitions are important to understand cell dynamics, and the maturation of liquid droplets is relevant to neurodegenerative disorders. We combined NMR and Raman spectroscopies with microscopy to follow, over a period of days to months, droplet maturation of the protein fused in sarcoma (FUS). Our study reveals that the surface of the droplets plays a critical role in this process, while RNA binding prevents it. The maturation kinetics are faster in an agarose-stabilized biphasic sample compared with a monophasic condensed sample, owing to the larger surface-to-volume ratio. In addition, Raman spectroscopy reports structural differences upon maturation between the inside and the surface of droplets, which is comprised of beta-sheet content, as revealed by solid-state NMR. In agreement with these observations, a solid crust-like shell is observed at the surface using microaspiration. Ultimately, matured droplets were converted into fibrils involving the prion-like domain as well as the first RGG motif.
  • Optimization of a blueprint for in vitro glycolysis by metabolic real-time analysis
    Item type: Journal Article
    Bujara, Matthias; Schümperli, Michael; Pellaux, Rene; et al. (2011)
    Nature Chemical Biology
  • Probing coenzyme A homeostasis with semisynthetic biosensors
    Item type: Journal Article
    Xue, Lin; Schnacke, Paul; Frei, Michelle; et al. (2022)
    Nature Chemical Biology
    Coenzyme A (CoA) is one of the central cofactors of metabolism, yet a method for measuring its concentration in living cells is missing. Here we introduce the first biosensor for measuring CoA levels in different organelles of mammalian cells. The semisynthetic biosensor is generated through the specific labeling of an engineered GFP–HaloTag fusion protein with a fluorescent ligand. Its readout is based on CoA-dependent changes in Förster resonance energy transfer efficiency between GFP and the fluorescent ligand. Using this biosensor, we probe the role of numerous proteins involved in CoA biosynthesis and transport in mammalian cells. On the basis of these studies, we propose a cellular map of CoA biosynthesis that suggests how pools of cytosolic and mitochondrial CoA are maintained.
  • Automatic policing of biochemical annotations using genomic correlations
    Item type: Journal Article
    Hsiao, Tzu-Lin; Revelles, Olga; Chen, Lifeng; et al. (2010)
    Nature Chemical Biology
  • Imaging and targeting LOX-mediated tissue remodeling with a reactive collagen peptide
    Item type: Journal Article
    Aronoff, Matthew R.; Hiebert, Paul; Hentzen, Nina B.; et al. (2021)
    Nature Chemical Biology
    Collagens are fibrous proteins that are integral to the strength and stability of connective tissues. During collagen maturation, lysyl oxidases (LOX) initiate the cross-linking of fibers, but abnormal LOX activity is associated with impaired tissue function as seen in fibrotic and malignant diseases. Visualizing and targeting this dynamic process in healthy and diseased tissue is important, but so far not feasible. Here we present a probe for the simultaneous monitoring and targeting of LOX-mediated collagen cross-linking that combines a LOX-activity sensor with a collagen peptide to chemoselectively target endogenous aldehydes generated by LOX. This synergistic probe becomes covalently anchored and lights up in vivo and in situ in response to LOX at the sites where cross-linking occurs, as demonstrated by staining of normal skin and cancer sections. We anticipate that our reactive collagen-based sensor will improve understanding of collagen remodeling and provide opportunities for the diagnosis of fibrotic and malignant diseases.
  • Quality control of disulfide bond formation in pilus subunits by the chaperone FimC
    Item type: Journal Article
    Crespo, Maria D.; Puorger, Chasper; Schärer, Martin A.; et al. (2012)
    Nature Chemical Biology
  • Structural and biochemical evidence for a boat-like transition state in beta-mannosidases
    Item type: Journal Article
    Tailford, Louise E.; Offen, Wendy A.; Smith, Nicola L.; et al. (2008)
    Nature Chemical Biology
Publications 1 - 10 of 65