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  • Natural products and synthetic bifunctional molecules enable the development of new chemical probes that target oxysterol-binding protein (OSBP), a key player in intracellular cholesterol homeostasis and Golgi complex integrity and a potential target for metabolic disease and cancer.

    • Po-Hsun Brian Chen
    • Jeremy M. Baskin
    News & Views
  • Identifying the protein component of calcium signaling in specific subcellular regions presents considerable challenges. Researchers have now successfully integrated calcium indicators with proximity labeling, enabling the targeting of microdomain-specific calcium signaling.

    • Yuki Ito
    • Tetsuya Takano
    News & Views
  • This Perspective proposes practical guidance to the application of AlphaFold2 for structure prediction of different classes of proteins including rigid globular proteins, intrinsically disordered proteins and alternative conformational states. The use of evaluation metrics to predict reliability of the resulting models and their integration with experimental data are also discussed.

    • Vinayak Agarwal
    • Andrew C. McShan
    Perspective
  • An efficient computational pipeline starting from validated peptide assemblies has been used to design two families of α-helical barrel proteins with functionalizable channels. This rationally seeded computational protein design approach delivers soluble, monomeric proteins that match the design targets accurately and with high success rates.

    • Katherine I. Albanese
    • Rokas Petrenas
    • Derek N. Woolfson
    ArticleOpen Access
  • An in vivo chemical screen has uncovered a potential role for a tryptophan metabolite in promoting host survival during bacterial infections through modulation of ionotropic glutamate receptors. Host-directed therapies for bacterial infections offer a largely untapped approach to treatment.

    • Mollie I. Sweeney
    • David M. Tobin
    News & Views
  • Biological nitrogen fixation requires low-potential electrons from ferredoxin or flavodoxin. Here the authors show how the soil diazotroph Azotobacter vinelandii employs the NADH:ferredoxin oxidoreductase RNF1 complex to lower the midpoint potential of the electron from NADH to reduce ferredoxin.

    • Lin Zhang
    • Oliver Einsle
    Article
  • The inaugural CRISPR-based drug Casgevy has been approved by several medical agencies, with other CRISPR-based therapies currently in clinical trials. Although there are technological hurdles to overcome, chemical biology has a vital role in developing recent breakthroughs in base editing, prime editing and epigenetic editing into future treatments.

    • Yitong Ma
    • Lei S. Qi
    Comment
  • The kinesin-1 motor protein accesses open active and closed autoinhibited states. These states are regulated by a flexible elbow within a complex coiled-coil architecture. Now, a conformational switch has been developed by engineering the elbow to create a closed state that can be controllably opened with a de novo designed peptide to increase kinesin transport inside cells.

    • Jessica A. Cross
    • William M. Dawson
    • Derek N. Woolfson
    ArticleOpen Access
  • Fluorogenic RNA aptamers have previously been developed to enhance RNA imaging. We determined the tertiary complex structures of a newly discovered Clivia aptamer, which exhibits a small size and a large Stokes shift. Structural insights into the fluorescence activation mechanism of Clivia build a strong foundation for its efficient use in RNA imaging.

    Research Briefing
  • Toxic small alarmone synthetase (toxSAS) enzymes are toxic effectors of certain toxin–antitoxin modules, involved in phage defense and secretion systems. Here the authors establish the mechanism underlying toxSAS inhibition by structured antitoxins and reveal the connection between neutralization strategy and substrate specificity.

    • Lucia Dominguez-Molina
    • Tatsuaki Kurata
    • Abel Garcia-Pino
    ArticleOpen Access
  • To understand the complex dynamics and diverse functions of RNA, robust technologies for labeling and imaging RNA are highly desirable. A newly developed green fluorescent aptamer named Okra enables the imaging of mRNA dynamics in living cells.

    • Dhrisya Sathyan
    • Murat Sunbul
    News & Views
  • Enediyne natural products are potent antitumor antibiotics but the biosynthesis of their 1,5-diyne-3-ene core has remained enigmatic for decades. Here a diiodotetrayne is reported as a universal enediyne biosynthetic intermediate of this core, obtained upon cryptic iodination.

    • Chun Gui
    • Edward Kalkreuter
    • Ben Shen
    Article