Volume 19 Issue 11, November 2023

A new platform for screening nucleophilic-fragment-based covalent ligands enables the identification and targeting of ligandable sulfenic acid sites, setting the stage for exploration of nucleophile-directed probe and drug development.

Brassinosteroid (BR) hormones promote root growth by controlling meristem size and cell elongation, but the mechanism of BR transport remains elusive. A new study shows that BR precursors move via intercellular pores called plasmodesmata to modulate BR cellular levels and their signaling functions.

Computational approaches are emerging as powerful tools for the discovery of antibiotics. A study now uses machine learning to discover abaucin, a potent antibiotic that targets the bacterial pathogen Acinetobacter baumannii.

CAG triple-nucleotide repeats in multiple genes have been linked to various human diseases. A recent study unveils the effects of CAG repeat RNA gelation on protein translation, thereby expanding our knowledge of CAG-elicited toxicities.

The quality of chemical tools and their appropriate use determine the quality and reliability of scientific data based on their use. Now, two papers extend criteria to new modalities and critically review adherence to established guidelines.

Chemoproteomics reveals a vast expanse of ligandable cysteine sulfenic acids in the human proteome, highlighting the utility of nucleophilic small molecules in the fragment-based covalent ligand discovery pipeline.

Determining which covalent binding events impact protein function is challenging. Now, a strategy has been reported that integrates base editing and chemical proteomics to infer the functionality of ligandable cysteines in cancer dependency proteins by quantifying the impact of their missense mutation on cancer cell proliferation.

Genetic and bioorthogonal chemistry approaches reveal cell-to-cell movement of brassinosteroid (BR) hormones via plasmodesmata in plants. In turn, BRs positively regulate callose deposition at plasmodesmata to balance its own biosynthesis.

Using a neural network trained on bacterial growth inhibition data, in silico prediction of molecules with activity against Acinetobacter baumannii led to the identification of the narrow-spectrum abaucin, which perturbs lipoprotein trafficking.

Cryo-EM structures of complement receptors C3aR and C5aR1 bound to their respective anaphylatoxin ligands C3a and C5a reveal insights into the conserved features and topological diversities of C3aR and C5aR1 in recognizing C3a and C5a.

Seo and Kleiner developed a small-molecule-dependent RNA editing platform termed TRIBE-ID to profile RNA–protein interactions in cells with temporal control and to study substrates of the stress granule protein G3BP1 during biomolecular condensation.

Pan, Lu, Feng, Lu et al. demonstrated that CAG repeat expansion RNAs can form gel-like condensates in the cytoplasm and sequester the translation elongation factor eEF2, leading to suppressed global protein synthesis and neurodegeneration-relevant phenotypes.

Wu, Liu, Zou et al. report an engineered hypercompact AsCas12f system, enAsCas12f, for robust and faithful genome editing in human cells. Cryo-EM study validates the engineering strategy and reveals dimerization-based substrate recognition by AsCas12f.

A probe for the ubiquitin-like protein Fubi led to the discovery of dual ubiquitin/Fubi C-terminal hydrolase activity in the deubiquitinase USP16 in addition to USP36, enabling structural characterization of this distinctive Ub/Ubl specificity, and revealed a synergistic role of USP16 in ribosomal protein maturation.

The flavoenzyme nicotine oxidoreductase degrades nicotine in the bloodstream. Now, genetic selection in bacteria has been used to improve the catalytic performance of nicotine oxidoreductase, isolating variants with increased O₂ reactivity that were more effective at degrading nicotine in the blood of rats.

Tryptophan hydroxylases have only been known from eukaryotes and are involved in the biosynthesis of serotonin or melatonin. Here, the authors characterize a family of bacterial tryptophan hydroxylases that differ markedly from their eukaryotic counterpart in cofactor and catalytic mechanism.

Peptide phage display reveals a non-catalytic binding site on the intervening domain of O-GlcNAc transferase. Its roles in substrate recognition, posttranslational modification (PTM) crosstalk and nutrient response provide insight into the function of this cryptic domain.