In-cell NMR suggests that DNA i-motif levels are strongly depleted in living human cells.

I-Motifs (iM) are non-canonical DNA structures potentially forming in the accessible, single-stranded, cytosine-rich genomic regions with regulatory roles. Chromatin, protein interactions, and intracellular properties seem to govern iM formation at sites with i-motif formation propensity (iMFPS) in human cells, yet their specific contributions remain unclear. Using in-cell NMR with oligonucleotide iMFPS models, we monitor iM-associated structural equilibria in asynchronous and cell cycle-synchronized HeLa cells at 37 °C.

High-Resolution Structure of RNA G-Quadruplex Containing Unique Structural Motifs Originating from the 5'-UTR of Human Tyrosine Kinase 2 (TYK2).

Tyrosine kinase 2 (TYK2) is a member of the JAK family of nonreceptor-associated tyrosine kinases together with highly homologous JAK1, JAK2, and JAK3 paralogues. Overexpression of TYK2 is associated with several inflammatory diseases, including severe complications during the COVID-19 infection. Since the downregulation of JAK paralogues could lead to serious health consequences or even death, it is critical to avoid it when designing drugs to suppress TYK2.

Comparative study of experimental and DFT calculations for 3-cinnamoyl 4-hydroxycoumarin derivatives.

Background: Computational research plays an important role in predicting the chemical and physical properties of biologically active compounds important in future structural modifications to improve or modify biological activity.

Objective: This research focuses on quantum chemical and spectroscopic investigations properties of synthesized 4-hydroxycoumarin derivatives.

Methods: Quantum chemical calculations were obtained using B3LYP, HF, and M06-2x level methods with the 6-31++G (d,p) basis set.

Dimeric structures of DNA ATTTC repeats promoted by divalent cations.

Structural studies of repetitive DNA sequences may provide insights why and how certain repeat instabilities in their number and nucleotide sequence are managed or even required for normal cell physiology, while genomic variability associated with repeat expansions may also be disease-causing. The pentanucleotide ATTTC repeats occur in hundreds of genes important for various cellular processes, while their insertion and expansion in noncoding regions are associated with neurodegeneration, particularly with subtypes of spinocerebellar ataxia and familial adult myoclonic epilepsy. We describe a new striking domain-swapped DNA-DNA interaction triggered by the addition of divalent cations, including Mg2+ and Ca2+.

Targeting the Main Protease (M, nsp5) by Growth of Fragment Scaffolds Exploiting Structure-Based Methodologies.

The main protease M, nsp5, of SARS-CoV-2 (SCoV2) is one of its most attractive drug targets. Here, we report primary screening data using nuclear magnetic resonance spectroscopy (NMR) of four different libraries and detailed follow-up synthesis on the promising uracil-containing fragment Z604 derived from these libraries. Z604 shows time-dependent binding.

Directed ultrafast conformational changes accompany electron transfer in a photolyase as resolved by serial crystallography.

Charge-transfer reactions in proteins are important for life, such as in photolyases which repair DNA, but the role of structural dynamics remains unclear. Here, using femtosecond X-ray crystallography, we report the structural changes that take place while electrons transfer along a chain of four conserved tryptophans in the Drosophila melanogaster (6-4) photolyase. At femto- and picosecond delays, photoreduction of the flavin by the first tryptophan causes directed structural responses at a key asparagine, at a conserved salt bridge, and by rearrangements of nearby water molecules.

Toxin:antitoxin ratio sensing autoregulation of the module.

The family of toxin-antitoxin (TA) operons is ubiquitous in bacterial genomes and, in , is an essential component to maintain the presence of chromosome II. Here, we show that transcription of the (Vc) operon is regulated in a toxin:antitoxin ratio-dependent manner using a molecular mechanism distinct from other type II TA systems. The repressor of the operon is identified as an assembly with a 6:2 stoichiometry with three interacting ParD2 dimers bridged by two ParE2 monomers.

DNA Quadruplex Structure with a Unique Cation Dependency.

DNA quadruplex structures provide an additional layer of regulatory control in genome maintenance and gene expression and are widely used in nanotechnology. We report the discovery of an unprecedented tetrastranded structure formed from a native G-rich DNA sequence originating from the telomeric region of Caenorhabditis elegans. The structure is defined by multiple properties that distinguish it from all other known DNA quadruplexes.

Setting new standards: Multiphasic analysis of microplastic mineralization by fungi.

Plastic materials provide numerous benefits. However, properties such as durability and resistance to degradation that make plastic attractive for variable applications likewise foster accumulation in the environment. Fragmentation of plastics leads to the formation of potentially hazardous microplastic, of which a considerable amount derives from polystyrene.

The collagen-like protein employs a unique binding mechanism for the recognition of host glycosaminoglycans.

Bacterial adhesion is a fundamental process which enables colonisation of niche environments and is key for infection. However, in , the causative agent of Legionnaires' disease, these processes are not well understood. The collagen-like protein (Lcl) is an extracellular peripheral membrane protein that recognises sulphated glycosaminoglycans (GAGs) on the surface of eukaryotic cells, but also stimulates bacterial aggregation in response to divalent cations.

Ultrafast Proton Conduction in an Aqueous Electrolyte Confined in Adamantane-like Micropores of a Sulfonated, Aromatic Framework.

Sulfonated, cross-linked porous polymers are promising frameworks for aqueous high-performance electrolyte-host systems for electrochemical energy storage and conversion. The systems offer high proton conductivities, excellent chemical and mechanical stabilities, and straightforward water management. However, little is known about mass transport mechanisms in such nanostructured hosts.

Biophysical characterization of the Plasmodium falciparum circumsporozoite protein's N-terminal domain.

The circumsporozoite protein (CSP) is the main surface antigen of the Plasmodium sporozoite (SPZ) and forms the basis of the currently only licensed anti-malarial vaccine (RTS,S/AS01). CSP uniformly coats the SPZ and plays a pivotal role in its immunobiology, in both the insect and the vertebrate hosts. Although CSP's N-terminal domain (CSP ) has been reported to play an important role in multiple CSP functions, a thorough biophysical and structural characterization of CSP is currently lacking.

Nuclear magnetic resonance analysis of extra virgin olive oil: classification through secoiridoids.

Background: Extra virgin olive oil (EVOO), a natural product with a multidisciplinary role, has been and is continuing to be studied from several points of view. Among them, its chemical analysis is of major importance and several methods have been used. Nuclear magnetic resonance (NMR) spectroscopy has inherent advantages, among them monitoring the chemical constituents without the need for a separation technique and without, for instance, possible carry-over effects.

Phytochemical Profile, Antioxidant Potential, Antimicrobial Activity, and Cytotoxicity of Dry Extract from Mill.

Dry rose extract (DRE) obtained industrially by aqueous ethanol extraction from flowers and its phenolic-enriched fraction, obtained by re-extraction with ethyl acetate (EAE) were the subject of this study. H NMR of DRE allowed the identification and quantitation of fructose and glucose, while the combined use of HPLC-DAD-ESIMS and HPLC-HRMS showed the presence of 14 kaempferol glycosides, 12 quercetin glycosides, 4 phenolic acids and their esters, 4 galloyl glycosides, 7 ellagitannins, and quinic acid. In addition, the structures of 13 of the flavonoid glycosides were further confirmed by NMR.

Ascorbate Peroxidase 2 (APX2) of Chlamydomonas Binds Copper and Modulates the Copper Insertion into Plastocyanin.

Recent phylogenetic studies have unveiled a novel class of ascorbate peroxidases called "ascorbate peroxidase-related" (APX-R). These enzymes, found in green photosynthetic eukaryotes, lack the amino acids necessary for ascorbate binding. This study focuses on the sole APX-R from referred to as ascorbate peroxidase 2 (APX2).

L.-Unrecognized Source of Phenylethanoid Glycosides: Green Extraction Approach and Elucidation of Phenolic Compounds via NMR and UHPLC-HR MS/MS.

Health-oriented preferences, a demand for innovative food concepts, and technological advances have greatly influenced changes in the food industry and led to remarkable development of the functional food market. Incorporating herbal extracts as a rich source of bioactive compounds (BC) could be an effective solution to meet the high demand of consumers in terms of expanding the high-quality range of functional foods. The aim of this study is the valorization of the bioactive potential of L.

Combined NMR and molecular dynamics conformational filter identifies unambiguously dynamic ensembles of Dengue protease NS2B/NS3pro.

The dengue protease NS2B/NS3pro has been reported to adopt either an 'open' or a 'closed' conformation. We have developed a conformational filter that combines NMR with MD simulations to identify conformational ensembles that dominate in solution. Experimental values derived from relaxation parameters for the backbone and methyl side chains were compared with the corresponding back-calculated relaxation parameters of different conformational ensembles obtained from free MD simulations.

A sodium/potassium switch for G4-prone G/C-rich sequences.

Metal ions are essential components for the survival of living organisms. For most species, intracellular and extracellular ionic conditions differ significantly. As G-quadruplexes (G4s) are ion-dependent structures, changes in the [Na+]/[K+] ratio may affect the folding of genomic G4s.

A Second Glass Transition Observed in Single-Component Homogeneous Liquids Due to Intramolecular Vitrification.

On supercooling a liquid, the viscosity rises rapidly until at the glass transition it vitrifies into an amorphous solid accompanied by a steep drop in the heat capacity. Therefore, a pure homogeneous liquid is not expected to display more than one glass transition. Here we show that a family of single-component homogeneous molecular liquids, titanium tetraalkoxides, exhibit two calorimetric glass transitions of comparable magnitude, one of which is the conventional glass transition associated with dynamic arrest of the bulk liquid properties, while the other is associated with the freezing out of intramolecular degrees of freedom.

Metabolomics revealed disruptions in amino acid and antioxidant biochemistry in Daphnia magna exposed to industrial effluents associated with plastic and polymer production.

Industrial wastewater effluents are a major source of chemicals in aquatic environments, and many of these chemicals may negatively impact aquatic life. In this study, the crustacean Daphnia magna, a common model organism in ecotoxicity studies, was exposed for 48 h to nine different industrial effluent samples from manufacturing facilities associated with the production of plastics, polymers, and coating products at a range of dilutions: 10, 25, 50, 100% (undiluted). A targeted metabolomic-based approach using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantify polar metabolites from individual daphnids that survived the 48 h exposure.

HR-MAS DREAMTIME NMR for Slow Spinning and Samples.

HR-MAS NMR is a powerful tool, capable of monitoring molecular changes in intact heterogeneous samples. However, one of the biggest limitations of H NMR is its narrow spectral width which leads to considerable overlap in complex natural samples. DREAMTIME NMR is a highly selective technique that allows users to isolate suites of metabolites from congested spectra.