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Etoposide, a chemotherapeutic poison of type IIA eukaryotic topoisomerases (topo IIs), promotes topo II to compact DNA by trapping DNA loops, creates DNA double-strand breaks, causes topo II to resist relocation, and pauses the ability of topoisomerases to relax DNA supercoiling. Through these mechanisms, etoposide converts topo II into a roadblock to DNA processing.
Using single-molecule biophysics methods, Le et al. discovered that etoposide, a chemotherapeutic poison of topoisomerase II (topo II), promotes topo II to compact DNA, trap DNA loops and pause DNA supercoiling relaxation, thus converting topo II into a strong roadblock to DNA processing.
A new biosynthetic core-forming enzyme, arginine cyclodipeptide synthase (RCDPS), was found to produce cyclo-arginine-Xaa dipeptides via a tRNA-dependent mechanism, and further genome mining using RCDPS as a beacon uncovered new natural products.
The multistep incorporation process of the catalytic NiFe(CN)2(CO) cofactor into [NiFe]-hydrogenase was deciphered by isolating key maturation intermediates, which were characterized by biochemical and a variety of spectroscopic techniques.
A bifunctional amino acid, photo-ANA, equipped with a bio-orthogonal handle and a photoreactive warhead, specifically labels Salmonella spp. during infection and enables the profiling of proteome dynamics and host–pathogen protein–protein interactions.
The F420-dependent sulfite reductase protects some methanogenic archaea by converting toxic sulfite. Structural analysis reveals how the two active centers are electro-connected and provides a plausible picture of a primitive sulfite reductase.
Development of two bright light-up RNA systems with strong aptamer–dye interaction, high fluorogenicity, and remarkable photostability, enable single-molecule mRNA tracking in live cells.
GPCRs are selective for specific G-protein subtypes, thereby ensuring signaling fidelity. A new report finds that that empty-like G-protein mutants are promiscuously recognized by GPCRs, suggesting that receptors select cognate over non-cognate G proteins at steps preceding nucleotide release.
Modern drug discovery relies upon intelligent exploration of ‘in stock’ and ‘on demand’ virtual libraries of compounds. A comparative analysis highlights the explosive expansion of accessible chemical space and also reveals challenges and opportunities arising for computational drug discovery.
The authors present a framework for multiplexed optimization of metabolic pathways based on CRISPR–dCas12a-mediated genetic circuits, which can be generally applied in the construction of microbial cell factories for sustainable bioproduction.
A near-atomic resolution strain-specific cryo-EM structure of infectious prion fibrils from mice was determined, revealing a structural definition for intra-species prion strain-specific conformations.
Coupling selectivity was found to be partly lost with G proteins that bypass conformations that exist before GDP release, suggesting that selectivity is closely linked to the process of nucleotide release.
Docking virtual libraries against protein structures has identified potent ligands for multiple targets. A comprehensive analysis reveals that the increased size of virtual libraries improves receptor fit but diverges from bio-like molecules.
Analysis of cell–cell communication between embryonic stem cells using a combination of experiments and modeling shows that cells can communicate important messages over much larger distances than previously known, exhibiting quorum-sensing-like behavior.
