375 papers
The authors developed and validated a robust, high-throughput fluorescence polarization assay using a novel tracer (KP-SC-1) to efficiently screen for both NAD+-dependent and independent SIRT1-3 inhibitors while significantly reducing enzyme consumption compared to previous methods.
This study identifies the known PRMT1 inhibitor AMI-1 as a potent NMNAT1 inhibitor, elucidates its mechanism of action through cryo-EM structural analysis, and demonstrates its efficacy in reducing nuclear NAD+ levels and viability in NMNAT1-dependent cancer cells, thereby validating NMNAT1 as a therapeutic target while cautioning against the off-target effects of AMI-1 in existing research.
This study presents the first cryo-EM structures of HIV-1 reverse transcriptase during polypurine tract strand displacement, revealing a unique 90-degree template flip mechanism mediated by specific residues (F61, R78, and W24) that offers a distinct structural target for developing next-generation antiretrovirals.
This study integrates thermal proteomics with a state-of-the-art graph neural network to identify Demethylzeylasteral as a direct ACLY inhibitor, validating its micromolar binding and demonstrating its therapeutic efficacy in treating psoriasis by reversing keratinocyte hyperproliferation and suppressing lipid metabolic reprogramming.
This study combines 10 microseconds of atomistic molecular dynamics simulations with in vitro experiments to reveal that short-lived contacts mediated by salt bridges, cation–π interactions, water, and Na+ ions govern the dynamics of MUT-16 condensates, which exhibit upper-critical solution temperature (UCST) phase behavior essential for germ granule formation and transposon silencing.
This study reveals that cardiac calsequestrin (CASQ2) is an intrinsic dimer that undergoes a highly cooperative, Ca2+-triggered polymerization switch modulated by K+ ions, providing a mechanistic framework for understanding how its mutations cause catecholaminergic polymorphic ventricular tachycardia type 2 through distinct pathological trajectories.
This study introduces a metatranscriptomic screening method based on ultrastable RNA secondary structures to uncover thousands of previously hidden ssRNA bacteriophages, demonstrating their potential as novel, engineerable capsid nanomaterials for RNA delivery and compiling them into a comprehensive database of over 460,000 RNA molecules and 100,000 coat proteins.
This study demonstrates that the transcription factor LSL-1 collaborates with chromatin regulators HIM-17, XND-1, and BRA-2 to establish the germline-specific transcriptional repertoire and safeguard germ cell fate in *C. elegans*.
This study overturns the prevailing paradigm that bile salt hydrolase (BSH) activity is exclusively mediated by Ntn cysteine hydrolases by discovering and characterizing a novel, broadly distributed class of metal-dependent BSHs (mBSHs) in the gut microbiome that specifically target taurine-conjugated bile acids.
This study demonstrates that the mitochondrial enzyme sulfide:quinone oxidoreductase (SQR) is essential for maintaining sulfur respiration, bioenergetics, and longevity across eukaryotes by oxidizing sulfide into supersulfides, as evidenced by impaired mitochondrial function and reduced lifespan in SQR-deficient yeast and mice models that could not be rescued by supersulfide supplementation.
This study demonstrates that high consumption of coffee decoction inhibits the nonhomologous end joining (NHEJ) DNA repair pathway by specifically targeting the Ligase IV/XRCC4 complex, leading to persistent DNA damage and suggesting potential implications for sensitizing tumors to genotoxic cancer therapies.
This study presents the 2.4 Å crystal structure of HIV-1 reverse transcriptase bound to the long-acting NNRTI depulfavirine, revealing an extended binding conformation that explains its potent activity against common resistant variants and its favorable additive or synergistic potential when combined with other antiretroviral agents.
This study demonstrates that fusing a bacterial microcompartment trimer with SpyTag enables its spontaneous self-assembly into robust, macroscopic layered protein materials that retain structural integrity and functional reactivity in both solution and dried states, offering a versatile platform for biointerfaces and sustainable protein engineering.
This study utilizes cryo-electron microscopy to reveal the structural architecture of the human inducible NOS holoenzyme in an active state, demonstrating how the reductase domain's FMN subdomain rotates to span the oxygenase dimer and position its cofactor near the heme to facilitate the essential electron transfer required for nitric oxide production.
This study demonstrates that protein kinase A mediates the glucagon-induced phosphorylation of UBE2J1 specifically at serine residue S266, a regulatory mechanism distinct from the S184 site and independent of the unfolded protein response, suggesting a novel role for UBE2J1 in integrating energy metabolism with cellular stress.
This study demonstrates that transposing an N-terminal biphenyl motif from full-length LL-37 onto short human cathelicidin derivatives significantly enhances their potency and stability against gram-negative bacteria by improving membrane permeabilization, offering a portable strategy to approximate the activity profile of the full-length peptide.
This study utilizes cryo-EM, molecular dynamics, and biochemical assays to reveal that DNA Ligase IIIα's ability to ligate single-strand breaks in nucleosomes is strictly dependent on the nick's translational position due to steric hindrance from the histone octamer, while the scaffolding protein XRCC1 does not significantly alter this activity.
This study presents a rapid, gentle protocol for isolating highly pure and functionally intact mitochondria from rodent cardiomyocytes using cell strainers instead of traditional mechanical homogenization, thereby preserving structural integrity and enabling diverse downstream applications such as patch-clamp electrophysiology and mitochondrial transplantation.
This study elucidates the structure, biosynthesis, and bioactivity of nostolysamides, a novel class of acylated lanthipeptides from *Nostoc punctiforme*, revealing their unique ring topology, the non-essential role of acylation for their membrane-disrupting antibacterial and antifungal activities, and the broad substrate specificity of the acyltransferase NpuN.
This study demonstrates that red and near-infrared light (620–820 nm) activates mitochondrial large-conductance calcium-activated potassium channels in glioblastoma cells, likely via cytochrome c oxidase, suggesting a potential non-pharmacological approach for cytoprotection.