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Evernimicin, an antibiotic of the orthosomycin class, inhibits bacterial translation by preventing ribosomes from polymerizing specific amino acid motifs, and controls the expression of resistance genes via such context-specific action.
Chemigenetic combination of a synthetic ion-recognition motif and a protein-based fluorophore resulted in the development of calcium and sodium ion sensors.
The combination of cryo-electron microscopy analysis with cell-signaling assays revealed promiscuous Gi/Gq coupling of somatostatin receptors and molecular mechanism of ligand-dependent selective G protein signaling
By inserting RNA-binding domains to an active-site-proximal loop amidst CRISPR–Cas, Yang, Song et al. generate variants with enhanced collateral activity for ultrasensitive and amplification-free RNA detection when coupled with electrochemical sensing platforms.
A new method for controlling NTP-driven reactions in single-molecule experiments via the local generation of NTPs (LAGOON) markedly increases the measurement throughput and enables single-turnover observations.
Enzymatically generated sulfane sulfur species called hydropersulfides terminate free radical chain reactions to prevent oxidative membrane damage and ferroptosis induction.
Polyketides are assembled by modular polyketide synthases and undergo chemical tailoring reactions. A dehydratase domain variant catalyzes two sequential elimination reactions from thioester intermediates to produce conjugated diene modifications.
Compound library screening combined with medicinal chemistry and structural biology approaches enables the development of potent and highly selective cell-permeable small-molecule inhibitors of phosphatidylinositol 3-kinase C2α activity and function.
Chemical proteomics identified covalent ligands targeting an isoform-restricted allosteric cysteine in JAK1. The compounds inhibit JAK1-dependent signaling in immune cells with unprecedented selectivity.
An RNA aptamer that selectively binds FAD over FADH2 shifted the reduction potential of the bound cofactor, similar to flavoproteins, and was shown through structural characterization to use π–π and donor–π interactions to drive the shift.
SARS-CoV-2 spike-directed, non-neutralizing antibodies were converted into broad-spectrum inhibitors by conjugation to the SARS-CoV-2 receptor, ACE2, resulting in fusion proteins that target all SARS-CoV-2 variants of concern tested.
A tool kit to study bacterial efflux pumps and the movement of compounds across the cell envelope was developed enabling investigation of efflux pump physiological functions, substrate specificities and profiling of efflux pump inhibitors.
Dynamic redundancy by horizontal gene transfer stabilizes gene abundances amidst compositional fluctuations in microbial communities, which suggests a means to program gene stability of complex microbiota.
Engineering of a high-affinity Delta-like variant, named DeltaMAX, potently activates Notch signaling when provided in a bead-bound or cellular format, while administration as a soluble decoy inhibits signaling.
Using methyl group and fluorine NMR spectroscopic methods, Overbeck et al revealed that the dynamics of the eukaryotic 5′→3′ exoribonuclease Xrn2 in the region around the active site are correlated with its catalytic activity.
Evybactin is an antimicrobial natural product that targets DNA gyrase, where it binds to a site overlapping with synthetic thiophene poisons and exerts selectivity for Mycobacterium tuberculosis via its transport mechanism into the cell.
Microtubule-associated proteins tau and MAP2 cooperatively form protein envelopes that compact the underlying tubulin lattice, revealing a novel role for these proteins in altering microtubule structure.
The description of the cryo-EM structure of an orphan adhesion GPCR–Gs protein complex in apo state facilitates the screening and identification of potential ligands of ADGRG2.
Using structural and biochemical methods, Liang et al. revealed a C-terminal glutamine-end recognition mechanism of TRIM7 E3 ligases, which enables identification of substrates for TRIM7 and provides insight into the versatile functions of TRIM7 in viral infection and the C-degron pathway.
Metabolic labeling experiments on fermenting yeast revealed that ethanol is oxidized to acetaldehyde and acetyl-CoA and is also a major source of NADH and NADPH, demonstrating that ethanol can be consumed as a TCA cycle and redox fuel.