Search

The authors present a genetically encoded tool based on a bifunctional enzyme that can regenerate NAD⁺ while executing an engineered glycerol shunt. The tool successfully restored redox imbalance and modulated lipid metabolism in vitro and in a mouse hepatic steatosis model.

Cells depend on early protein modifications for proper function. Here, the authors show that when Src-family signaling kinases lack their typical myristoylation, an alternative acetylated start is detected by DCAF10, directing them to degradation.

Here, the authors found that human NAT16 acetylates histidine in vitro and in vivo. Biochemical and structural characterisation uncovered a double-GNAT fold with distinct active site architecture that is conserved across species.

Boosting mitochondrial metabolism in neurons in central memory circuits by enhancing Ca²⁺ retention in the mitochondrial matrix is shown to improve long-term memory formation in flies and mice.

Phytic acid chelates essential minerals, reducing their bioavailability in cereal-based diets. This study proposes a scalable, species-independent chemical approach that targets myo-inositol 3-phosphate synthase 1 (INO1), a key enzyme in phytic acid biosynthesis, to lower its levels in rice and wheat without affecting plant growth or yield.

The 1913 study ‘Die Kinetik der Invertinwirkung’, by Michaelis and Menten, marked a pivotal advancement in enzymology by illustrating the application of mechanistic models and quantitative kinetics to biocatalysis. The foundational framework described back then continues to have a strong impact on enzymology, with profound influences that range from undergraduate education to structure–function studies and the format and content of contemporary kinetic databases.

The magnitudes of replenishment and priming, two important but opposing fluxes in soil organic carbon (SOC) dynamics, have not been compared. Here the authors show that the magnitude of replenishment is greater than that of priming, resulting in a net SOC accumulation after additional carbon input to soils.

While Prussian blue (PB) nanozymes are typically employed as antioxidants, their reactive oxygen species-generating capability remains unexplored. Here, the authors predict by molecular dynamics and identify explicit hydroxyl radical generation in highly crystalline cesium-doped PBs.

Through local pH buffering, biomolecular condensates can expand the optimal pH interval for enzymatic reactions, increasing robustness to changes in solution pH and enabling network reactions with enzymes that require different pH conditions.

DNA damage tolerance is regulated by ubiquitination of PCNA. Here, the authors present kinetic and structural studies showing that USP1/UAF1 prefers trimming K63- and K48-ubiquitin chains down over cleavage of monoubiquitinated PCNA. Mutant analysis suggests evolutionary preservation of this mechanism.

Enzymes adapt by sampling new conformations while balancing destabilizing effects of mutations. Here, the authors reveal how TEM-1 β-lactamase acquires cefotaxime resistance through reshaping of dynamic conformational ensembles and localized stability networks, offering insight into the molecular framework of the activity-stability tradeoff.

Large-scale computational and in vitro analyses identify commensal type III secretion systems and substrates in the human gut microbiome that can interact with human proteins to modulate immune pathways.

Here the authors applied cryogenic time-resolved electron microscopy with rapid UV photolysis of a caged substrate to elucidate the catalytic mechanism of lipid-sugar transfer within the bacterial membrane by the glycosyltransferase GtrB.

A rationally designed assay detects granzyme A activity by integrating peptide-based GzmA-targeted inhibitors and probes with chemiluminescent reporters to monitor inflammatory bowel disease.

Coenzyme Q has several important biological functions, but the understanding of the biosynthesis of coenzyme Q in humans remains incomplete. Now, by constructing the entire COQ metabolon in vitro, the enzymes and reactions underlying coenzyme Q biosynthesis are characterized.

Nanozymes often suffer from self-depletion, limiting their long-term efficacy for practical applications. Here, the authors report Cu-Fe twincrystal nanozymes that leverage the continuous electron-donating role of Cu²⁺ ions to achieve sustain enzymatic activity and prolonged antifungal effects.

CRISPR-based diagnostics are often limited by complex workflows and poor validation. Here the authors develop and validate a one-pot asymmetric CRISPR assay, which permits rapid and sensitive diagnosis of tuberculosis in a format which is suitable for resource-limited settings.

Li, Burgos-Bravo and colleagues report that NDF phase separation regulates FACT condensation, which enhances transcription by generating a localized biochemical environment that promotes nucleosome disassembly while preserving chromatin integrity by retaining histones.

Using synthesized experimental and observational data, Cen et al. revealed that anthropogenic nitrogen deposition has increased global forest soil CO₂ emissions by ~5%, despite considerable spatial variation in the effects of nitrogen deposition.

Here they demonstrate a mechanism that converts analog stress stimuli into digital JNK activation, allowing organisms to make binary cell-fate decisions that avoid harmful reactions to mild stress while enabling robust responses to strong stress.

PIN transporters are key players in distributing phenoxyacetic acid herbicides. Mutagenesis and cryo-EM structures elucidate substrate specificity and transport mechanisms, paving the way for improved synthetic auxin development and herbicide-resistant crops.

Multi-enzymatic cascades benefit from precise nanometric organization but achieving this using available scaffolds is challenging. Here the authors present strategy for organizing multienzymatic systems using a protein scaffold based on TRAP domains, and demonstrate improved catalytic output.

How RNA folds into functional structures is still largely uncharacterized. Here, using cryo-EM, SAXS, and molecular dynamics (MD) simulations, the authors create a movie of a medically relevant ribozyme acquiring its functionally active conformation.

APOBEC3A mutates its host DNA in human cancers to evolve drug resistance. Modified-DNA inhibitors suppress this mutagenic activity in cells, suggesting use as conjuvants in anti-cancer therapies. Here the authors reveal structural insights into how these inhibitors bind APOBEC3A.

We present a computational approach to the design of high-efficiency enzymes with catalytic parameters comparable to natural enzymes, enabling programming of stable, high-efficiency, new-to-nature Kemp elimination enzymes through minimal experimental effort.

Plastic-degrading enzymes can be utilized for plastic recycling. Here, QM/MM molecular dynamics and experimental Michaelis–Menten kinetics provide insight into PETase/MHTase activities of the lipase B from Candida antartica.

Catalytic mechanisms of enzymes are well understood, but achieving diverse reaction chemistries in re-engineered proteins can be difficult. Here the authors show a highly efficient and thermostable artificial enzyme that catalyzes a diverse array of substrate oxidations coupled to the reduction of H₂O₂.

The emergence of novel catalytic functions in ancient proteins likely played a role in the evolution of modern enzymes. Here, the authors use protein sequences from Precambrian beta-lactamases and demonstrate that a single hydrophobic-to-ionizable amino acid mutation can lead to substantial Kemp eliminase activity.

The folding-dependent catalytic behavior of enzymes is of fundamental biological importance, yet mechanistically underexplored. Here, the authors show that an α-helix, commonly found in proteins, can facilitate its own growth through the self-catalyzed polymerization of N-carboxyanhydride in solvents with low polarity.

The Eyes Absent proteins (EYA1-4) are a group of tyrosine phosphatases. Here, the authors report a signalling pathway in which EYA4 and EYA1 dephosphorylate Polo-like kinase 1 (PLK1) at pY445 to support PLK1 activation and mitosis.

Designer enzymes comprising an abiological molecule incorporated into a natural protein have been reported, but the use of proteins as ligands to construct abiological (multinuclear) metal centers is rare. Here, the authors report a designer multi-metalloenzyme with extrinsic and intrinsic functions obtained by grafting a synthetic trinuclear zinc complex inside a human cytokine macrophage migration inhibitory factor scaffold.

Mg-protoporphyrin IX monomethyl ester cyclase catalyses the formation of the isocyclic ring in the synthesis of chlorophyll. Kinetic analyses and mass spectrometry identified intermediates in the reaction.

Allostery produces concerted functions of protein complexes by orchestrating the cooperative work between the constituent subunits. By restoring functions of pseudo-active sites that have been lost through evolution, allosteric sites have now been designed into a rotary molecular motor, V₁-ATPase, resulting in its rotation being boosted allosterically.

Removing Mg²⁺ from RNA and replacing it with Fe²⁺ confers on some RNAs the ability to catalyse single-electron transfer. Here, it is hypothesized that Fe²⁺ was an RNA cofactor on the early Earth, when iron was benign and abundant, and was replaced by Mg²⁺ during a period known as the great oxidation, brought on by photosynthesis.

A metabolic system of engineered biocatalysts using the noncanonical cofactor nicotinamide mononucleotide is established for biomanufacturing in cell-free systems and in Escherichia coli without interference from nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate.

Carbonic anhydrase (CA) mimics have promising applications in the enhanced hydration and sequestration of CO₂, but limited success has so far been achieved. Here, the authors report the assembly of sequence-defined peptoids into crystalline nanomaterials with controlled microenvironment of active sites as CA mimics for promoted hydration and sequestration of CO₂.

In eukaryotes, dynamins and dynamin-like proteins (DLPs) are involved in various membrane remodeling processes. Here, the authors present the structure and functional characterization of a DLP of the cyanobacterium Synechocystis sp. PCC 6803.

Hydroxylysine galactosylation is essential for collagen maturation. This work reveals the molecular structure of human GLT25D1, its catalytic residues, and a noncatalytic structural domain stabilized by metal ion and donor substrate binding.

TRIM5α is an E3 ligase that inhibits retroviral replication. Here, the authors delineate the biochemical mechanism that accelerates N terminal autoubiquitylation of TRIM5α upon its association with the retroviral capsid and, thus, enables recognition of an infection-associated molecular pattern.

A number of mechanisms are known to mediate bacterial antibiotic resistance. Here, Arad et al show that amyloid fibrils produced by Staphylococcus aureus rapidly degrade common antibiotic molecules.

This study identifies E167, Y268, and Q269 as drug-resistant hotspots for SARS-CoV papain-like protease inhibitors that bind to the BL2 loop and groove region, which are valuable in informing the design of the next-generation PLpro inhibitors.

Second messengers regulate a broad spectrum of processes in bacteria. Here, authors characterize how the second messenger cyclic di-AMP inhibits the potassium transporter KimA using cryo-EM, molecular dynamics simulations and functional assays.

While glucose homeostasis in the circulation is tightly controlled by insulin and other hormones, dedicated hormonal regulators do not exist for most other circulating metabolites. Using perturbative metabolite infusions with isotope labelling in mice, Li et al. show that homeostasis of many circulating metabolites is considerably regulated through mass action-driven oxidation.

Rashan, Bartlett and colleagues show that mammalian 4-hydroxy fatty acids are primarily catabolized by ACAD10 and ACAD11 (atypical mitochondrial and peroxisomal acyl-CoA dehydrogenases, respectively) that use phosphorylation in their reaction mechanisms.

Asparaginyl endopeptidases (AEPs) catalyze the cyclization step during the biosynthesis of cyclic peptides in plants. Here, the authors report a recombinantly produced AEP that catalyzes the backbone cyclization of a linear cyclotide precursor and an engineered analog with high efficiency and in a pH-dependent manner.

Heparan sulfate biosynthesis is a complex process involving multiple reactions that extend and modify the polysaccharide. Here, the authors resolve structures of NDST1, responsible for the critical N-sulfoglucosamine modification of heparan sulfate.