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  • Targeted protein degradation has emerged as a promising approach in drug discovery, harnessing a cell’s intrinsic machinery to eliminate disease-related proteins. Now, a study paves the way to translating this technology into potential anti-mycobacterial therapies, by exploiting the bacterial protein-degradation complex.

    • Delia Preti
    • Valentina Albanese
    • Peggy Carla Raffaella Marconi
    News & Views
  • Engineered living materials harness the computational power of biology to control interesting material properties. Here the authors leverage complex transcriptional regulation of bacterial extracellular electron transfer to control hydrogel cross-linking with Boolean logic.

    • Austin J. Graham
    • Gina Partipilo
    • Benjamin K. Keitz
  • Reliably identifying ubiquitin ligase interactors and substrates has been a persistent challenge in cellular biology. A breakthrough comes in the form of a potent, selective and cell-active chemical probe, shedding light on the intricate functions of a key regulatory enzyme.

    • Shaoshuai Xie
    • Gang Li
    News & Views
  • Owens et al. reported PFI-7, a selective and potent antagonist of GID4 of the CTLH E3 ligase complex, which enables identification of human GID4 targets. This study provides valuable insights into GID4 functions and a powerful tool for advancing new targeted protein degradation strategies.

    • Dominic D. G. Owens
    • Matthew E. R. Maitland
    • Cheryl H. Arrowsmith
  • A newly developed maternally selective nanobody antagonist against the angiotensin II type I receptor stabilizes the receptor in a hybrid conformation and simultaneously binds with specific small-molecule antagonists.

    • Meredith A. Skiba
    • Sarah M. Sterling
    • Andrew C. Kruse
  • Biochemical pathways for aromatic amino acid synthesis are ancient and highly conserved. Directed evolution of the β-subunit of tryptophan synthase (TrpB)—a proficient biocatalyst that converts indole to l-tryptophan—enabled this enzyme to make l-tyrosines from phenols, a pathway not (yet) known in nature.

    • Patrick J. Almhjell
    • Kadina E. Johnston
    • Frances H. Arnold
  • Natural ribozymes can cleave RNA and single-stranded DNA (ssDNA) by transesterification or a blend of hydrolytic and transesterification reactions. Now, ribozymes have been discovered that catalyze the hydrolytic cleavage of ssDNA. Similar ribozymes could potentially replace large, immunogenic, protein-based nucleases in gene therapies.

    • Madeleine B. King
    • Audrone Lapinaite
    News & Views
  • Ferroptosis, a cell death mechanism induced by lipid peroxidation, is pivotal in tumor suppression. A recent study shows that tumor repopulating cells evade ferroptosis and develop resistance to therapy via subverting a lipid metabolism enzyme.

    • Yuelong Yan
    • Boyi Gan
    News & Views
  • We present a discovery pipeline integrating chemical fragment screening and time-resolved, high-throughput small-angle X-ray scattering (TR-HT-SAXS). This approach identifies allosteric chemical leads targeting distinct allosteric states of the mitochondrial oxidoreductase apoptosis-inducing factor (AIF). By monitoring kinetic rates of allosteric transition with TR-HT-SAXS, we link fragment structure–activity relationships (SARs) to biomolecular conformation.

    Research Briefing
  • CRISPR–Cas13 systems use single-subunit RNA-guided Cas13 effectors for targeted RNA recognition and cleavage. This Review summarizes the recent advances in understanding the structural and mechanistic aspects of Cas13 systems and the diverse applications of these systems in biotechnology and therapeutics.

    • Hui Yang
    • Dinshaw J. Patel
    Review Article