388 papers
This study demonstrates that perturbing fumarate metabolism in *Plasmodium berghei* leads to cysteine succination and oxidative stress, which specifically impairs ookinete formation while sparing erythrocytic stages, thereby highlighting parasite-specific fumarate hydratase as a promising target for transmission-blocking antimalarial drugs.
This study identifies over 100 proteins involved in forming toxic ROS-induced DNA-protein crosslinks (ROS-DPCs) in human cells and elucidates how the ubiquitin-proteasomal system, SPRTN metalloprotease, and nucleotide excision repair pathways collaborate to remove these lesions, while also demonstrating that a stable glutathione analog can prevent their formation as a potential therapeutic strategy.
This paper presents a modular platform that utilizes compound-dependent or nanobody-mediated induced proximity to rapidly screen and identify effective acetyltransferase effectors for site-specific lysine acetylation of diverse protein substrates in living cells, thereby accelerating the development of targeted chemical probes for post-translational modification editing.
This study reveals that the membrane-anchored foldase LipH from *Pseudomonas aeruginosa* utilizes intrinsic conformational dynamics and membrane interactions to transiently occlude its chaperone cavity, thereby balancing the initial capture and folding of the LipA lipase via its MD2 domain with the subsequent release of the mature client to facilitate efficient secretion.
This study demonstrates that a modular -barrel domain swapping strategy applied to -hemolysin generates stable chimeric nanopores with tailored transport properties, significantly enhancing single-molecule sensing capabilities for nucleic acids and proteins.
This study presents the first cryo-EM structure of full-length TECPR1, revealing an elongated hook-shaped architecture with cis-oriented Dysferlin domains stabilized by a novel tectonin-PH interface that provides a structural framework for its role in noncanonical autophagy.
This study utilizes pharmacological profiling and genomic editing to demonstrate that while DGK inhibitors like R59022 and BMS-502 exhibit paralog-specific effects on DGKalpha, effective reduction of phosphatidic acid levels during PLC signaling requires the simultaneous inhibition of both DGKalpha and phospholipase D enzymes.
This study introduces ChlorON-1-PRO, a bright, high-affinity all-optical sensor engineered via a single C139N mutation to enable real-time imaging of chloride transport dynamics in living cells.
This study demonstrates that integrating cyclic traveling-wave ion mobility spectrometry with laser-assisted rapid evaporative ionization mass spectrometry (LA-REIMS) significantly enhances molecular resolution and chemical specificity in ambient biofluid metabolomics by effectively filtering matrix interferences, resolving isomers, and enabling high-throughput, chromatography-free metabolic fingerprinting.
This paper presents a solid-phase synthesis strategy for fluorogenic ProTide probes that enables ultrasensitive profiling of carboxypeptidase activities, revealing specific enzymatic signatures in human blood that distinguish pancreatic cancer patients from healthy controls.
This study presents the rational design and optimization of virus-inspired lipid nanoparticles with refined ionizable lipid content that achieve superior intracellular delivery and functional genome editing via CRISPR/Cas ribonucleoprotein complexes, including successful transport across a brain endothelial barrier model.
This study reports the heterologous production and characterization of a self-sufficient Clade E carbon monoxide dehydrogenase (CpBC1CODH-III) from *Clostridium pasteurianum* BC1, demonstrating that while its co-expression with the CooCTJ maturation machinery stabilizes the enzyme, its catalytic activity is primarily limited by nickel availability rather than maturation efficiency.
Researchers discovered a novel dual thiobarbiturate-indole compound (MDOLL-0273) that selectively inhibits the chikungunya virus nsP3 macrodomain by binding to a cryptic pocket, offering a promising starting point for developing antiviral therapies against CHIKV.
This study presents the crystal structure and biochemical characterization of ORF11, a bifunctional tail-spike lysin from an *E. faecium* podovirus that uniquely combines N-acetylglucosaminidase and D,D-endopeptidase activities to facilitate bacterial cell wall degradation during infection.
This study identifies semicarbazone and thiosemicarbazone analogs, particularly compound 25, as promising noncovalent competitive inhibitors of the SARS-CoV-2 main protease (Mpro) through a combined approach of virtual screening targeting an allosteric site, biochemical validation, and molecular dynamics simulations.
This study characterizes three newly discovered nylon hydrolases (Nyl10, Nyl12, and Nyl50), revealing their tetrameric structures, substrate-induced conformational changes in active site loops, and identifying Nyl12 as the most promising candidate for engineering efficient PA66 degradation.
This study utilizes computational mass spectrometry and genome mining to discover novel metallophores (bulbichelins and extended petrobactins) produced by *Microbulbifer* in mono-culture, while revealing that these compounds are suppressed in co-culture with a coral pathogen, suggesting the bacterium employs alternative iron acquisition strategies like siderophore piracy in mixed communities.
The Q-MOL platform is a validated, high-fidelity in silico drug discovery system that overcomes the limitations of traditional methods by effectively treating protein flexibility and identifying binding sites on diverse targets—including rigid, flexible, and intrinsically disordered proteins as well as RNA—without requiring pre-defined structural pockets.
This study reveals that lysosomal cysteine cathepsins catalyze reverse proteolysis to generate non-genomically templated fusion peptides, including T1D-associated autoantigens, thereby uncovering a previously unrecognized pathway for peptide diversification and immune activation.
This study utilizes time-resolved cryo-electron microscopy to reveal how the E3 ligase UBE3C reprograms the 26S proteasome by creating a shortcut for ubiquitin shuttling that bypasses the deubiquitylase USP14, thereby allosterically enhancing unfolding forces to degrade ultra-stable protein aggregates implicated in neurodegeneration.