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  • Mutant-selective KRAS-targeting drugs hold great promise for the treatment of some of the most aggressive forms of cancer. Building on the breakthrough success of KRAS-G12C inhibitors, researchers have now found a way to target another mutant KRAS with serine-modifying covalent inhibitors.

    • Micah J. Niphakis
    • Benjamin F. Cravatt
    News & Views
  • A directed evolution approach delivers ribosomes with highly functional tethered subunits. Combining the decoding and peptidyl transferase activities of the ribosome into a single entity sets the scene for more efficient protein engineering technologies.

    • Aleksandra Filipovska
    • Oliver Rackham
    News & Views
  • Using single-molecule magnetic tweezers and biochemical methods, Naqvi et al. revealed how CRISPR–Cas12a regulates the DNA cleavage rate through a conserved stacking interaction between the R-loop and the W355 residue and the sequence of the CRISPR RNA 3′ end.

    • Mohsin M. Naqvi
    • Laura Lee
    • Mark D. Szczelkun
    Article Open Access
  • The de novo design of a pair of complementary peptides, one basic for cell penetration and target binding and one acidic that can be fused to proteins of interest, provides an approach for delivery into mammalian cells and subcellular targeting.

    • Guto G. Rhys
    • Jessica A. Cross
    • Derek N. Woolfson
    Article
  • A combination of engineering a fluorine-selective trans-acyltransferase and manipulation of the fluorinated extender unit pool in Escherichia coli enables the production of site-selectively fluorinated erythromycin precursors in vitro in vitroin vitro and in vivo.

    • Sasilada Sirirungruang
    • Omer Ad
    • Michelle C. Y. Chang
    Article
  • A combined screening and selection approach enables the evolution of the generalist transcription factor RamR into specific and sensitive biosensors for various alkaloids and in turn a streamlined pathway for tetrahydropapaverine biosynthesis.

    • Simon d’Oelsnitz
    • Wantae Kim
    • Andrew D. Ellington
    Article
  • Functional screening of a large metagenomic library with a droplet microfluidics platform enabled the discovery of SN243, a bacterial β-glucuronidase from the glycoside hydrolase 3 family, which was characterized structurally and biochemically.

    • Stefanie Neun
    • Paul Brear
    • Florian Hollfelder
    Article
  • The Hippo pathway is a key regulator of tissue homeostasis, organ size and cancer. Identification of microcolin B and its analog molecules as Hippo pathway activators connects PtdIns4P-dependent lipid signaling with the Hippo pathway, suggesting potential targets for cancer therapy.

    • Gayoung Seo
    • Wenqi Wang
    News & Views
  • Aldehyde dehydrogenase 1B1-specific small-molecule inhibitors are identified that block the growth of colon cancer spheroids and organoids and are shown to potentially regulate mitochondrial metabolism and ribosomal function.

    • Zhiping Feng
    • Marisa E. Hom
    • James K. Chen
    Article