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The susceptibility of nitric oxide (NO) to scavenging and oxidation limits its bioavailability and signaling role. New studies indicate that a NO–ferroheme adduct is resistant to such constraints and may serve as an alternative NO-derived signaling molecule in vasculature.
Newly developed synthetic antibodies offer the means to be used as high-affinity, conformation-specific probes to capture dynamic repertoires of neddylated cullin–RING E3 ligase complexes. This allows nonenzymatic profiling of the diverse signaling networks that are based on these active complexes.
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.
A universally effective method has been developed to enable cryo-electron microscopy structural determination of G protein–coupled receptors in various states. This method will accelerate structure-based drug discovery and enhance understanding of the activation mechanism for these receptors.
The development of biosensors has been slowed by the optimization required for each new iteration. Now, the ChemoX platform facilitates the expansion of sensor design, resulting in unique Förster resonance energy transfer pairings with versatile applications and optimized readouts.
Cryo-EM structures of chemical-compound-bound α-synuclein amyloid fibrils shed light on the mechanism by which small molecules bind to cross-beta-sheet amyloid structures, opening the gateway to rational drug design for targeting pathological amyloid assemblies.
Modular polyketide synthases are multidomain megasynthases catalyzing polyketide chain elongation, modification and release. New work reveals a full ~360-kDa modular polyketide synthases with just one active domain, ketosynthase, catalyzing an amidation that releases the completed product (a reaction type typically catalyzed by dedicated thioesterases).
A study has now shown that copper ions can drive inflammation via a mitochondrial signaling pathway that regulates epigenetic states of immune cells. This pathway could offer a new route for treating inflammatory diseases.
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.
Medicinal drugs can cross-react with gut bacterial proteins, but the identification of these off-target interactions is difficult. Multi-omic approaches enabled the discovery of a bacterial peptidase that is inhibited by diabetic drugs and unexpectedly influences bacterial fitness within complex microbial communities via a non-proteolytic mechanism.
New biochemical and structural studies into the capsule biosynthesis pathway of Haemophilus influenzae serotype b (Hib) provide invaluable insights into a unique, basket-shaped multi-modular enzymatic machinery, allowing accelerated development of fermentation-free production methods for Hib glycoconjugate vaccine.
Lysosomal hyperacidification is regarded as a hallmark of autophagy. A new pH nanosensor that detects shifts in near-infrared emission bands is used to quantify cellular and intratumoral lysosomal pH.
High-throughput analysis of translation arrest sites and structural studies reveal tetracenomycin X as a selective protein synthesis inhibitor, acting predominantly at distinct sequence motifs. The drug may be developed as an antibiotic or for treatments based on halting the expression of individual proteins.
Sodium bisulfite is widely used in methylation sequencing, yet it degrades DNA, and on its own, it does not discriminate methylated cytosine from its oxidized derivative, 5-hydroxymethylcytosine. A new bisulfite-free technique uses enzymatic modification of DNA for direct and accurate methylation mapping.
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.
Tricyclic peptides have reduced conformational flexibility, making them well suited for ligand development. Researchers have now generated large combinatorial libraries of tricyclic peptides using a disulfide-directing motif. Screening these libraries discovered binders to challenging protein targets.
Anaerobes have developed unique metabolic pathways and strategies, some of which are still not well understood. Now, a study that integrates spectroscopy with dynamic metabolic modeling reveals the metabolism of the anaerobic pathogen Clostridioides difficile.
The mechanisms responsible for replicative misincorporation of an adenine into DNA opposite 8-oxoguanine (8OG) remain obscure. A new study suggests that 8OG redistributes the balance between several mispair conformations, enabling the high rates of misincorporation of adenine paired with 8OG by DNA polymerases.
Bacterial biofilms are resilient multicellular communities with spatially complex localized interactions that remain largely uncharacterized. A new approach called RainbowSeq enables transcriptional profiling in biofilms with increased spatial resolution.
