Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Predicting prospective drug-like molecules quickly and accurately is a considerable challenge for de novo drug design. An interactome-based deep learning method has been developed that outperforms standard chemical language models.
The paenilamicins are hybrid nonribosomal peptide–polyketide compounds that inhibit protein synthesis. Here the authors reveal that paenilamicins bind to a unique site on the ribosome, where they interfere with the translocation of mRNA and tRNAs during elongation.
Fucosylation of host glycoproteins is revealed to sensitize cells to cholera intoxication while fucosylation of host glycolipids is protective. The glycosyltransferases encoded by B3GALT5 and B3GNT5 are identified as key regulators of this phenomenon.
Development of a targeted protein degradation platform, methylarginine targeting chimera (MrTAC), enables arginine methylation-driven degradation of intracellular proteins in lysosomes.
Prokaryotic CRISPR–Cas systems are counteracted by phage-encoded anti-CRISPR elements, and how they protect themselves remains enigmatic. A study shows that CRISPR-repressed toxins defend CRISPR–Cas against anti-CRISPR proteins or RNAs by inducing abortive infection.
Metabolic engineering often suffers from competition between heterologous enzymes and native metabolism. Here the authors improve on a strategy of compartmentalizing metabolic pathways to the peroxisome by increasing peroxisome functional capacity, aided by machine learning, to produce geraniol.
High levels of superoxide (O2•–) are known to regulate plant stem cell behavior, but its downstream effectors remain unclear. O2•– was found to directly promote DNA demethylase ROS1 activity to maintain the stemness of plant shoot apical meristem.
Using site-specific chemical crosslinking strategies, Ai, Tong and Deng et al. captured structural intermediates of ubiquitin E3 ligase RNF168-mediated H2A K13 and K15 monoubiquitination and adjacent dual monoubiquitination in the DNA damage repair response; the structural analysis revealed a helix-anchoring mechanism.
Protein kinase C (PKC) enzymes are critical signaling molecules but their regulation at emerging signaling hubs is unclear. Here Su et al. develop a sensitive fluorescent biosensor, ExRai-CKAR2, and reveal distinct spatiotemporal regulation of different PKC isoforms in two-dimensional and three-dimensional models.
Biofouling causes a huge economic loss to our society. This Perspective examines the biofouling process from microfouling to macrofouling, discusses a spectrum of chemical signals that induce and inhibit biofouling and argues for potential management by targeting the signaling responsible for biofilm dispersion or biofouling inhibition.
This Perspective discusses how macromolecular condensation can regulate the electrochemistry to affect biological function in living cells and provides a framework to study the electrochemical functions of biomolecular condensates.
A nanopore-based framework distinguishes and quantifies tyrosine sulfation from phosphorylation in peptide mixtures and native protein fragments and determines the sequence of the sulfated fragment.
The integration of a new orthogonal redox cofactor opens opportunities for controlling reaction equilibria. Because it does not interfere with cellular redox homeostasis, this approach enables the precise tuning of metabolic pathways and the optimization of microbial bioproduction, independently of canonical redox balancing.
An automation tool has been designed that enables partitioning of an algorithm into subcircuits split across cells for biological computing. The tool was applied to a hashing algorithm requiring 110 logic gates across 66 cells.
The use of an adenine base editor enables identification of functional serine, threonine and tyrosine residues that impact cell fitness on a genome-wide scale with possible involvement in phosphorylation, structural maintenance and cancer biology.
Research in the early days of chemical biology was mostly limited to the application of chemical tools to model cell lines grown in incubators. Now, discoveries are being made in more physiologically relevant systems, from tissues to organisms, using precisely targeted molecules. The 2023 Chemical Biology & Physiology meeting (in Portland, Oregon) discussed the latest advances in the field, with research from around the globe demonstrating that the transition to making discoveries at the chemical biology–physiology interface is happening now.
Orally bioavailable, high molecular weight macrocyclic peptides that inhibit difficult-to-drug protein–protein interactions are of high therapeutic value, and rules for their design were proposed recently. Here, we emphasize the danger of rules that provide a false impression of the lipophilicity required of a clinical candidate.
A tRNA modification, named 2-aminovaleramididine (ava2C), has been discovered in plant organelles and bacteria. Structural analysis shows specific codon recognition by this modification, highlighting the evolutionary diversity of the essential tRNA modifications.
Li, Cheng, Yu and colleagues have discovered a Cas13j family, including the compact and highly efficient LepCas13j (529 aa) and ChiCas13j (424 aa), with promising applications in RNA editing in vivo.
