Cyclic Olefin Copolymer-Based Fixed-Target Sample Delivery Device for Protein X-ray Crystallography.

Serial macromolecular X-ray crystallography plays an important role in elucidating protein structures and consequently progressing the field of targeted therapeutics. The use of pulsed beams at different repetition frequencies requires the development of various sample-conserving injection strategies to minimize sample wastage between X-ray exposures. Fixed-target sample delivery methods that use solid support to hold the crystals in the X-ray beam path are gaining interest as a sample-conserving delivery system for X-ray crystallography with high crystal hit rates.

The microbiota metabolite, phloroglucinol, confers long-term protection against inflammation.

Phloroglucinol is a key byproduct of gut microbial metabolism that has been widely used as a treatment for irritable bowel syndrome. Here, we demonstrate that phloroglucinol tempers macrophage responses to pro-inflammatory pathogens and stimuli. , phloroglucinol administration decreases gut and extraintestinal inflammation in murine models of inflammatory bowel disease and systemic infection.

Marine emissions of methanethiol increase aerosol cooling in the Southern Ocean.

Ocean-emitted dimethyl sulfide (DMS) is a major source of climate-cooling aerosols. However, most of the marine biogenic sulfur cycling is not routed to DMS but to methanethiol (MeSH), another volatile whose reactivity has hitherto hampered measurements. Therefore, the global emissions and climate impact of MeSH remain unexplored.

Heterogenous Chemistry of IO as a Critical Step in Iodine Cycling.

Global iodine emissions have been increasing rapidly in recent decades, further influencing the Earth's climate and human health. However, our incomplete understanding of the iodine chemical cycle, especially the fate of higher iodine oxides, introduces substantial uncertainties into atmospheric modeling. IO was previously deemed a "dead end" in iodine chemistry; however, we provide atomic-level evidence that IO can undergo rapid air-water or air-ice interfacial reactions within several picoseconds; these reactions are facilitated by prevalent chemicals on seawater such as amines and halide ions, to produce photolabile reactive iodine species such as HOI and IX (X = I, Br, and Cl).

The ALS drug riluzole binds to the C-terminal domain of SARS-CoV-2 nucleocapsid protein and has antiviral activity.

Nucleoproteins (N) play an essential role in virus assembly and are less prone to mutation than other viral structural proteins, making them attractive targets for drug discovery. Using an NMR fragment-based drug discovery approach, we identified the 1,3-benzothiazol-2-amine (BZT) group as a scaffold to develop potential antivirals for SARS-CoV-2 nucleocapsid (N) protein. A thorough characterization of BZT derivatives using NMR, X-ray crystallography, antiviral activity assays, and intrinsic fluorescence measurements revealed their binding in the C-terminal domain (CTD) domain of the N protein, to residues Arg 259, Trp 330, and Lys 338, coinciding with the nucleotide binding site.

New insights into the function and molecular mechanisms of Ferredoxin-NADP reductase from Brucella ovis.

Bacterial ferredoxin(flavodoxin)-NADP reductases (FPR) primarily catalyze the transfer of reducing equivalents from NADPH to ferredoxin (or flavodoxin) to provide low potential reducing equivalents for the oxidoreductive metabolism. In addition, they can be implicated in regulating reactive oxygen species levels. Here we assess the functionality of FPR from B.

Calibration of Arctic ice core bromine enrichment records for past sea ice reconstructions.

Bromine in ice cores has been proposed as a qualitative sea ice proxy to produce sea ice reconstructions for the polar regions. Here we report the first statistical validation of this proxy with satellite sea ice observations by combining bromine enrichment (with respect to seawater, Br) records from three Greenlandic ice cores (SIGMA-A, NU and RECAP) with satellite sea ice imagery, over three decades. We find that during the 1984-2016 satellite-era, ice core Br values are significantly correlated with first-year sea ice formed in the Baffin Bay and Labrador Sea supporting that the gas-phase bromine enrichment processes, preferentially occurring over the sea ice surface, are the main driver for the Br signal in ice cores.

Structural Insights and Reaction Profile of a New Unspecific Peroxygenase from Produced in a Tandem-Yeast Expression System.

Fungal unspecific peroxygenases (UPOs) are gaining momentum in synthetic chemistry. Of special interest is the UPO from (UPO), which shows an exclusive repertoire of oxyfunctionalizations, including the terminal hydroxylation of alkanes, the α-oxidation of fatty acids and the C-C cleavage of corticosteroids. However, the lack of heterologous expression systems to perform directed evolution has impeded its engineering for practical applications.

Innovative Strategies in X-ray Crystallography for Exploring Structural Dynamics and Reaction Mechanisms in Metabolic Disorders.

Enzymes are crucial in metabolic processes, and their dysfunction can lead to severe metabolic disorders. Structural biology, particularly X-ray crystallography, has advanced our understanding of these diseases by providing 3D structures of pathological enzymes. However, traditional X-ray crystallography faces limitations, such as difficulties in obtaining suitable protein crystals and studying protein dynamics.

Evaluating the potential of non-immunosuppressive cyclosporin analogs for targeting Toxoplasma gondii cyclophilin: Insights from structural studies.

Toxoplasmosis persists as a prevalent disease, facing challenges from parasite resistance and treatment side effects. Consequently, identifying new drugs by exploring novel protein targets is essential for effective intervention. Cyclosporin A (CsA) possesses antiparasitic activity against Toxoplasma gondii, with cyclophilins identified as possible targets.

Application of terpenoids for the remediation of environmental water polluted with bisphenol A and its analogs using an in silico approach.

Nowadays, there is a global concern over water quality and the impact of contamination on both natural ecosystems and human well-being. Plastics, ubiquitous in modern life, may release harmful chemicals when they reach aquatic environments. Among them, bisphenol A (BPA) and its alternatives, such as bisphenol S (BPS), bisphenol F (BPF), and others, are of special concern because their presence in water systems can have detrimental effects on human health and aquatic organisms due to their endocrine-disrupting properties.

Ochratoxinase Is a Highly Specific, Metal-Dependent Amidohydrolase Suitable for OTA Biodetoxification in Food and Feed.

Microbial enzymes can be used as processing aids or additives in food and feed industries. Enzymatic detoxification of ochratoxin A (OTA) is a promising method to reduce OTA content. Here, we characterize the full-length enzyme ochratoxinase (OTA), an amidohydrolase from .

MAX-DOAS observations of ship emissions in the North Sea.

Shipping emissions were measured in Dunkirk, France. Elevated aerosol extinction coefficients (AEC), nitrogen dioxide (NO) and sulphur dioxide (SO) were observed up to 500 m from surface. Formaldehyde (HCHO) did not show an increase every time, which suggests that oxidation of emitted volatile organic compounds (VOCs) took longer than the transport to the observation path and dilution of direct emissions had occurred.

Spontaneous Molecular Bromine Production in Sea-Salt Aerosols.

Bromine chemistry is responsible for the catalytic ozone destruction in the atmosphere. The heterogeneous reactions of sea-salt aerosols are the main abiotic sources of reactive bromine in the atmosphere. Here, we present a novel mechanism for the activation of bromide ions (Br) by O and HO in the absence of additional oxidants.

Oligomeric Structure of Yeast and Other Invertases Governs Specificity.

Invertases, or β-fructofuranosidases, are metabolic enzymes widely distributed among plants and microorganisms that hydrolyze sucrose and release fructose from various substrates. Invertase was one of the earliest discovered enzymes, first investigated in the mid-nineteenth century, becoming a classical model used in the primary biochemical studies on protein synthesis, activity, and the secretion of glycoproteins. However, it was not until 20 years ago that a member of this family of enzymes was structurally characterized, showing a bimodular arrangement with a β-propeller catalytic domain, and a β-sandwich domain with unknown function.

Molecular and structural basis of oligopeptide recognition by the Ami transporter system in pneumococci.

ATP-binding cassette (ABC) transport systems are crucial for bacteria to ensure sufficient uptake of nutrients that are not produced de novo or improve the energy balance. The cell surface of the pathobiont Streptococcus pneumoniae (pneumococcus) is decorated with a substantial array of ABC transporters, critically influencing nasopharyngeal colonization and invasive infections. Given the auxotrophic nature of pneumococci for certain amino acids, the Ami ABC transporter system, orchestrating oligopeptide uptake, becomes indispensable in host compartments lacking amino acids.

New insights into the domain of unknown function (DUF) of EccC, the pivotal ATPase providing the secretion driving force to the ESX-5 secretion system.

Type VII secretion (T7S) systems, also referred to as ESAT-6 secretion (ESX) systems, are molecular machines that have gained great attention due to their implications in cell homeostasis and in host-pathogen interactions in mycobacteria. The latter include important human pathogens such as Mycobacterium tuberculosis (Mtb), the etiological cause of human tuberculosis, which constitutes a pandemic accounting for more than one million deaths every year. The ESX-5 system is exclusively found in slow-growing pathogenic mycobacteria, where it mediates the secretion of a large family of virulence factors: the PE and PPE proteins.

Typhoon- and pollution-driven enhancement of reactive bromine in the mid-latitude marine boundary layer.

Tropospheric reactive bromine is important for atmospheric chemistry, regional air pollution, and global climate. Previous studies have reported measurements of atmospheric reactive bromine species in different environments, and proposed their main sources, e.g.

Structural and functional analysis of the key enzyme responsible for the degradation of ochratoxin A in the Alcaligenes genus.

The potential to degrade ochratoxin A (OTA), a highly poisonous mycotoxin, was investigated in cultures from Alcaligenes-type strains. Genome sequence analyses from different Alcaligenes species have permitted us to demonstrate a direct, causal link between the gene coding a known N-acyl-L-amino acid amidohydrolase from A. faecalis (AfOTH) and the OTA-degrading activity of this bacterium.

Linear epitopes of bony fish β-parvalbumins.

Introduction: Fish β-parvalbumins are common targets of allergy-causing immunity. The nature of antibody responses to such allergens determines the biological outcome following exposure to fish. Specific epitopes on these allergens recognised by antibodies are incompletely characterised.