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Stepwise assembly of the active site of [NiFe]-hydrogenase

Nature Chemical Biology, Published online: 26 January 2023; doi:10.1038/s41589-022-01226-wThe 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.

Photo-ANA enables profiling of host–bacteria protein interactions during infection

Nature Chemical Biology, Published online: 26 January 2023; doi:10.1038/s41589-022-01245-7A 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.

Genome mining for unknown–unknown natural products

Nature Chemical Biology, Published online: 26 January 2023; doi:10.1038/s41589-022-01246-6A 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.

Avidity-based bright and photostable light-up aptamers for single-molecule mRNA imaging

Nature Chemical Biology, Published online: 19 January 2023; doi:10.1038/s41589-022-01228-8Development 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.

Structures of the sulfite detoxifying F<sub>420</sub>-dependent enzyme from <i>Methanococcales</i>

Nature Chemical Biology, Published online: 19 January 2023; doi:10.1038/s41589-022-01232-yThe 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.

Stickier G-protein conformations

Nature Chemical Biology, Published online: 16 January 2023; doi:10.1038/s41589-022-01239-5GPCRs 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...

The ‘Big Bang’ of the chemical universe

Nature Chemical Biology, Published online: 16 January 2023; doi:10.1038/s41589-022-01233-xModern 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...

Modeling the expansion of virtual screening libraries

Nature Chemical Biology, Published online: 16 January 2023; doi:10.1038/s41589-022-01234-wDocking 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.

CRISPR–dCas12a-mediated genetic circuit cascades for multiplexed pathway optimization

Nature Chemical Biology, Published online: 16 January 2023; doi:10.1038/s41589-022-01230-0The 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.

The role of G protein conformation in receptor–G protein selectivity

Nature Chemical Biology, Published online: 16 January 2023; doi:10.1038/s41589-022-01231-zCoupling 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.

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