Search Results (527)

Flavor, as one of the primary factors that attracts consumers, has always been a crucial indicator for evaluating the quality of food. From processing to final consumption, the conditions that affect consumers’ perception of the aroma of aquatic products can be divided into three stages: aroma formation, release, and signal transmission. Currently, there are few reviews on the formation, release, and perception of aroma in aquatic products, which has affected the product development of aquatic products. This review summarizes aroma formation pathways, the effects of processing methods, characteristic volatile compounds, various identification techniques, aroma-release influencing factors, and the aroma perception mechanisms of aquatic products. The Maillard reaction and lipid oxidation are the main pathways for the formation of aromas in aquatic products. The extraction, identification, and quantitative analysis of volatile compounds reveal the odor changes in aquatic products. The composition of aquatic products and oral processing mainly influence the release of odorants. The characteristic odorants perceived from the nasal cavity should be given more attention. Moreover, the relationship between various olfactory receptors (ORs) and the composition of multiple aromatic compounds remains to be understood. It is necessary to clarify the relationship between nasal cavity metabolism and odor perception, reveal the binding and activation mode of ORs and odor molecules, and establish an accurate aroma prediction model. Full article

Endometriosis is a disorder characterized by the presence of endometrial tissue outside the uterus, leading to dyspareunia, chronic pelvic pain, dysuria, and infertility. The latter has been related to implantation failure associated with alterations in decidualization, a process regulated by sex hormones such as progesterone. Membrane progesterone receptor β (mPRβ) exhibits a lower expression in endometriotic tissues than in normal endometrial ones. However, the role of mPRβ in decidualization is unknown. This work aimed to investigate whether mPRβ plays a role in the decidualization of endometrial stromal cells (ESCs) derived from women with and without endometriosis. The mPR agonist OrgOD-2 induced the gene expression of key decidualization markers (insulin-like growth factor binding protein 1, prolactin, transcription factor heart and neural crest derivatives-expressed transcript 2, and fork-head transcription factor) in healthy ESCs, eutopic (uterine cavity), and ectopic (outside of the uterine cavity) ESCs from women with endometriosis. Notably, the expression of the decidualization markers was lower in endometriotic cells than in healthy endometrial ones. An siRNA mediated knockdown of mPRβ reduced the expression of decidualization-associated genes in ESCs treated with a decidualization stimuli, regardless of whether cells were derived from healthy women or those with endometriosis. Our data suggest that progesterone, through mPRβ activation, regulates the decidualization process in endometrial stromal cells from women with and without endometriosis. Full article

A series of rivastigmine hybrids, incorporating rivastigmine fragments (RIV) and a set of different antioxidant scaffolds, were designed, synthesized, and evaluated as multifunctional agents for the potential therapy of Alzheimer’s disease (AD). In vitro bioactivity assays indicated that some compounds have very good antioxidant (radical-scavenging) activity. The compounds also displayed good inhibitory activity against cholinesterases, though the bigger-sized hybrids showed higher inhibitory ability for butyrylcholinesterase (BChE) than for acetylcholinesterase (AChE), due to the larger active site cavity of BChE. All the hybrids exhibited an inhibition capacity for self-induced amyloid-β (Aβ_1–42) aggregation. Furthermore, cell assays demonstrated that some compounds showed capacity for rescuing neuroblastoma cells from toxicity induced by reactive oxygen species (ROS). Among these RIV hybrids, the best in vitro multifunctional capacity was found for the caffeic acid derivatives enclosing catechol moieties (4AY5, 4AY6), though the Trolox derivatives (4AY2, 4BY2) presented the best cell neuroprotective activity against oxidative damage. Molecular-docking studies provided structural insights into the binding modes of RIV-based hybrids to the cholinesterases, revealing key interaction patterns despite some lack of correlation with inhibitory potency. Overall, the balanced multifunctional profiles of these hybrids render them potentially promising candidates for treating AD, thus deserving further investigation. Full article

Infections with cytomegalovirus (CMV) can result in increased morbidity and mortality in immunocompromised patients. The pUL97 kinase is a critical enzyme in the regulation of CMV replication. Although it does not phosphorylate deoxynucleosides, this enzyme is involved in the first phosphorylation step of ganciclovir (GCV), a viral DNA polymerase inhibitor. In contrast, maribavir (MBV) is a specific inhibitor of pUL97 kinase activity. In this paper, we analyzed the already-reported amino acid changes, conferring resistance to MBV and cross-resistance to GCV, in the pUL97 protein structure, predicted with AlphaFold2. Docking experiments suggest that MBV is a dual-site inhibitor, targeting ATP binding and substrate phosphorylation. Substitutions that confer resistance to MBV only may directly or indirectly alter the shape of the cavity in the vicinity of the invariant K355 in the putative ATP binding site, without affecting the viral growth. The most frequently encountered T409M substitution may correspond to a gatekeeper mutation. Substitutions that induce cross-resistance to MBV and GCV may directly or indirectly affect the environment of D456 and N461 residues in the catalytic loop, with reduced viral replicative capacity. These results have implications for the clinical use of MBV as well as for the design of novel pUL97 kinase inhibitors. Full article

Steroids are found in bacteria and eukaryotes, and genes potentially encoding steroid metabolic enzymes have also been identified in giant viruses. For decades, hydroxylated steroids have been utilized in medicine to treat various human diseases. The hydroxylation of steroids can be achieved using microbial enzymes, especially cytochrome P450 monooxygenases (CYPs/P450s) and is well documented. Understanding the structural determinants that govern the regio- and stereoselectivity of steroid hydroxylation by P450s is essential in order to fully exploit their potential. Herein, we present a comprehensive analysis of the steroid-hydroxylating CYP109 family across the domains of life and delineate the structural determinants that govern steroid hydroxylation. Data mining, annotation, and phylogenetic analysis revealed that CYP109 family members are highly populated in bacteria, and indeed, these members passed from bacteria to archaea by horizontal gene transfer, leading to the evolution of P450s in archaea. Analysis of twelve CYP109 crystal structures revealed large, flexible, and dynamic active site cavities that can accommodate multiple ligands. The correct positioning and orientation of the steroid in the active site cavity and the nature of the C17 substituent on the steroid molecule influence catalysis. In an analogous fashion to the CYP107 family, the amino acid residues within the CYP109 binding pocket involve hydrophilic and hydrophobic interactions, influencing substrate orientations and anchoring and determining the site of hydroxylation and catalytic activity. A handful of amino acids, such as Val84, Val292, and Ser387 in CYP109B4, have been found to play a role in determining the catalytic regiospecificity, and a single amino acid, such as Arg74 in CYP109A2, has been found to be essential for the enzymatic activity. This work serves as a reference for the precise understanding of CYP109 structure–function relationships and for P450 enzymes in general. The findings will guide the genetic engineering of CYP109 enzymes to produce valuable steroid molecules of medicinal and biotechnological importance. Full article

Recently, it has been proposed that plant melatonin receptors belong to the superfamily of G protein-coupled receptors (GPCRs). However, a detailed description of the phylogeny, protein structure, and binding properties of melatonin, which is still lacking, can help determine the signaling and function of this compound. Melatonin receptor homologs (PMTRs) were identified in 90 Viridiplantae sensu lato proteomes using profile Hidden Markov Models (HMM), which yielded 174 receptors across 87 species. Phylogenetic analysis revealed an expansion of PMTR sequences in angiosperms, which were grouped into three clades. Docking studies uncovered a conserved internal melatonin-binding site in PMTRs, which was analogous to the site in human MT1 receptors. Binding affinity simulations indicated this internal site exhibits stronger melatonin binding compared to a previously reported superficial pocket. Ligand–receptor interaction analysis and alanine scanning highlighted a major role of hydrophobic interactions, with hydrogen bonds contributing predominantly at the internal site, while non-interacting charged residues stabilize the binding pocket. Tunnel and ligand transport simulations suggested melatonin moves favorably through the internal cavity to access the binding site. Also, we presented for the first time details of these pockets in a non-model species, Capsicum chinense. Taken together, the structural analyses presented here illustrate opportunities and theoretical evidence for performing structure–function studies via mutations in specific residues within the proposed new melatonin-binding site in PMTRs, shedding light on their role in plant melatonin signaling. Full article

Neurotransmitters such as serotonin regulate key physiological and cognitive functions, yet real-time detection remains challenging due to the limitations of conventional techniques like amperometry and microdialysis. Fluorescent molecularly imprinted polymer nanoparticles (fMIP-NPs) offer a promising alternative and are typically synthesized via solid-phase synthesis, in which template molecules are covalently immobilized on a solid support to enable site-specific imprinting. However, strong template–template interactions during this process can compromise selectivity. To overcome this, we incorporated a poly(methacrolein-co-methacrylamide)-based template anchoring strategy to minimize undesired template interactions and enhance imprinting efficiency. We optimized the synthesis of poly(methacrolein-co-methacrylamide) under three different conditions by varying the monomer compositions and reaction parameters. The poly(methacrolein-co-methacrylamide) synthesized under Condition 3 (5:1 methacrolein-to-methacrylamide molar ratio, 1:150 initiator-to-total monomer ratio, and 4.59 M total monomer concentration) yielded the most selective fMIP-NPs, whose fluorescence intensity increased with an increase in serotonin concentration, rising by up to 37% upon serotonin binding. This improvement is attributed to higher aldehyde functionality in the poly(methacrolein-co-methacrylamide) which enhances template immobilization and generates a rigid imprinted cavity to interact with serotonin. These findings suggest that the developed fMIP-NPs hold significant potential as imaging probes for neurotransmitter detection, contributing to advanced studies in neural network analysis. Full article

The complexation of nabumetone (NAB) and naproxen (NAP) with cucurbit[7]uril (CB7) was investigated in aqueous solution by isothermal titration microcalorimetry, mass spectrometry, NMR spectroscopy, and computation methods. High-resolution mass spectrometry was used for the determination of the binding stoichiometry and the gas-phase stability of the drug–CB7 complex. The doubly charged NH₄⁺ or Na⁺ adducts of the 1:1 complex were observed in the mass spectra. The dissociation of complexes was monitored at different collision energies, (1–16) eV, leading to the neutral loss of NH₃ and the drug, with charge retention observed on CB7. By performing ITC experiments, all the thermodynamic parameters were determined for the NAB-CB7 complex in water at 25 °C. The corresponding values amounted to the following: logK = 4.66 ± 0.01; Δ_rG° = −26.7 ± 0.1 kJ/mol; Δ_rH° = −20.2 ± 0.7 kJ/mol; TΔ_rS° = 6.4 ± 0.8 kJ/mol, i.e., the formation of the inclusion complex is enthalpy driven and has a favorable entropy. The inclusion phenomena were further confirmed by NMR spectroscopy (¹H, ROESY, and DOSY), suggesting the encapsulation of the naphthalene ring of both drugs inside the CB7 cavity. The results of the DFT calculations and the IGMH analysis were in accordance with the experimental ones, suggesting that van der Waals interactions play a major role in drug–CB7 complexation. Full article

Molecularly imprinted polymers (MIPs) are synthetic polymers designed to exhibit selective recognition and binding capabilities toward target molecules and have been widely combined with advanced ceramic-based materials toward better performance in many catalytic applications of interest and beyond. What sets MIPs apart is their molecularly imprinted cavities, which are formed during polymerization in the presence of a template molecule. Upon template removal, these cavities retain the shape, size, and chemical functionality of the template molecule, allowing for highly specific recognition and binding of target molecules. In recent years, there has been a growing interest in leveraging these molecularly imprinted cavities not only for molecular recognition and sensing but also as catalytic sites and supports. Complementary to experimental studies, density functional theory (DFT) calculations are increasingly used to elucidate the molecular interactions, catalytic mechanisms, and optimize the design of MIP–ceramic catalysts. This review aims to provide a comprehensive overview of the current state of research on advanced ceramic-based catalysts supported by MIPs for environmental applications. Additionally, the review will discuss challenges and future directions in the field, focusing on enhancing the catalytic efficiency, stability, and scalability of MIP-based ceramic catalysts. By exploring these aspects, this review seeks to illustrate the promising role of MIP-modified ceramic materials in advancing the field of catalysis and catalytic supports. Full article

This study successfully developed a novel molecularly imprinted ultrafiltration membrane (MIUM) for energy-efficient and selective removal of dibutyl phthalate (DBP) from wastewater. Guided by Gaussian simulations, methacrylic acid (MAA) was identified as the optimal functional monomer, achieving the strongest binding energy (ΔE = −0.0698 a.u.) with DBP at a 1:6 molar ratio, providing a foundation for precise cavity construction. DBP-imprinted polymers (MIPs) synthesized via bulk polymerization were integrated into polysulfone membranes through phase inversion. The optimized MIUM (81.27% polymer content) exhibited exceptional performance under low-pressure operation (0.2 MPa), with a water flux of 111.49 L·m²·h⁻¹ and 92.87% DBP rejection, representing a 43% energy saving compared to conventional nanofiber membranes requiring 0.4 MPa. Structural characterization confirmed synergistic effects between imprinted cavities and membrane transport properties as the key mechanism for efficient separation. Notably, MIUM demonstrated remarkable selectivity, achieving 91.57% retention for DBP while showing limited affinity for structurally analogous phthalates (e.g., diethyl/diisononyl phthalates). The membrane maintained > 70% retention after 10 elution cycles, highlighting robust reusability. These findings establish a paradigm for molecular simulation-guided design of selective membranes, offering an innovative solution for low-energy removal of endocrine disruptors. The work advances wastewater treatment technologies by balancing high permeability, targeted pollutant removal, and operational sustainability, with direct implications for mitigating environmental risks and improving water quality management. Full article

Chemosensory proteins (CSPs) are small soluble proteins found predominantly in insects, with a conserved structure that contains a hydrophobic cavity. While originally associated with chemosensation, they were soon implicated to several other functions related to their ability to bind hydrophobic molecules. Research in the last decade has shown that CSPs may play a role in insecticide resistance. Several CSP genes are upregulated upon induction by sublethal insecticide doses or are highly expressed in resistant populations. RNA interference of CSP genes can restore susceptibility to insecticides. In vitro binding assays and molecular docking simulations suggest that CSPs can strongly bind to insecticides and can accommodate even large molecules in their hydrophobic cavities. Some cases of CSP overexpression in transgenic insects conferring insecticide resistance are reported. Taken together, these results indicate a role for CSPs in insecticide resistance, presumably through a sequestration mechanism, perhaps in combination with other mechanisms like metabolic resistance. This article reviews the evidence for CSP involvement in resistance and discusses ongoing research in the field. Full article

In this work, the possibility of enhancing the antioxidant capacity of whey protein (WP) through non-covalent interaction with methyl hesperidin (MH, a hesperidin derivative) was assessed. The underlying mechanism was analyzed in terms of multi-spectroscopy methods, thermodynamic analysis, and molecular docking simulation. The data indicated that MH could spontaneously bind to WP and form a non-fluorescent complex when physically mixed together. The presence of MH statically quenched the intrinsic fluorescence of WP, changed the microenvironment of amino acid residue, and altered the secondary and tertiary structure of WP, which in turn enhanced the antioxidant capacity of WP. The underlying mechanism may be assigned to hydrophobic interactions, which promoted MH inserting itself into the hydrophobic cavity in WP. The methoxy group on the B ring of MH may form hydrogen bonds with amino acids, which enhances the freedom of the phenyl hydroxyl group, resulting in higher antioxidant capacity than other hesperidin structural analogs. This research would enrich the theoretical basis about the interaction between protein and hesperidin-based derivatives, and it may supply valuable information for its application in the food and medicine fields. Full article

Comparative studies using lysophosphatidic acid (LPA) and the synthetic agonist, oleoyl-methoxy glycerophosphothionate (OMPT), in cells expressing the LPA₃ receptor revealed differences in the action of these agents. The possibility that more than one recognition cavity might exist for these ligands in the LPA₃ receptor was considered. We performed agonist docking studies exploring the whole protein to obtain tridimensional details of the ligand–receptor interaction. Functional in cellulo experiments using mutants were also executed. Our work includes blind docking using the unrefined and refined proteins subjected to hot spot predictions. Distinct ligand protonation (charge −1 and −2) states were evaluated. One LPA recognition cavity is located near the lower surface of the receptor close to the cytoplasm (Lower Cavity). OMPT displayed an affinity for an additional identification cavity detected in the transmembrane and extracellular regions (Upper Cavity). Docking targeted to Trp102 favored binding of both ligands in the transmembrane domain near the extracellular areas (Upper Cavity), but the associating amino acids were not identical due to close sub-cavities. A receptor model was generated using AlphaFold3, which properly identified the transmembrane regions of the sequence and co-modeled the lipid environment accordingly. These two models independently generated (with and without the membrane) and adopted essentially the same conformation, validating the data obtained. A DeepSite analysis of the model predicted two main binding pockets, providing additional confidence in the predicted ligand-binding regions and support for the relevance of the docking-based interaction models. In addition, mutagenesis was performed of the amino acids of the two detected cavities. In the in cellulo studies, LPA action was much less affected by the distinct mutations than that of OMPT (which was almost abolished). Therefore, docking and functional data indicate the presence of distinct agonist binding cavities in the LPA₃ receptor. Full article

Methylmalonic acidemia (MMA) is a genetic condition associated with intellectual disability and a high mortality rate. It is caused by pathogenic variants in the MMUT gene, which codes methylmalonyl-CoA mutase enzyme (MUT). In the Mexican population, the variant NM_000255.4:c.322C>T or p.(Arg108Cys) is the most frequently found, but its structural pathogenic effect is scarcely studied. To describe the clinical picture of p.(Arg108Cys) homozygous patients and to predict its structural pathogenic effect, we performed an analysis of the medical files from six MMA Mexican p.(Arg108Cys) homozygous patients. The structural changes in MUT caused by this variant were analyzed through molecular dynamics simulations (MDS) and docking and compared with the wild-type (Wt) enzyme. The main clinical symptoms presented by the patients were feeding difficulties, lethargy, and neurodevelopmental delay, with a predominance of early-onset phenotype and a mortality rate of 83%. We found significant structural changes in MUT structure, particularly in the catalytic domain, with increased volume cavity, shortening of the binding substrate tunnel, and aberrant accommodation. Also, the dimerization interface area increased from 1343 Ų in the Wt to 3386 Ų, and the dimer formation involved a different set of amino acids. The NM_000255.4:c.322C>T or p.(Arg108Cys) MMUT variant is associated with a severe outcome in MMA Mexican patients, and the enzyme was associated with ostentatious topological changes in the secondary and tertiary structure, which impacted the catalytic domain, the accommodation of the substrate, and the dimerization interface. Further ex vivo functional studies are needed to confirm these predictions, such as enzymatic activity measurements in fibroblasts of patients. Full article

Background/Objectives: Microcolins A–M are cytotoxic marine lipopeptides produced by the cyanobacterium Moorena producens, also known as Lyngbya majuscula. Recent studies have shown that two compounds in the series, microcolins B and H, can form covalent complexes with phosphatidylinositol transfer proteins α and β (PITPα/β) upon the reaction of their α,β-unsaturated ketone group with the thiol group of a key cysteine residue of PITP. These observations prompted us to compare the binding of all microcolins and a few related derivatives (VT01454 and (deoxy)majusculamide D) to PITP to delineate structure–binding relationships. Methods: A molecular docking analysis led to the identification of microcolin E as the potentially best PITPα binder in the series, followed by microcolins B and H and analog VT01454. The computational data agree well with the published experimental results. Results: The binding of microcolin H into a large cavity of PITPα positions its reactive electrophilic α,β-unsaturated ketone close to the thiol of Cys95, enabling the facile formation of a covalent C-S linkage. A similar bonding can occur with the Cys94 of PITPβ. Molecular models of microcolins bound to PITP were compared to identify structural elements chiefly implicated in the recognition process. Conclusions: This computational study provides guidance in the design of microcolin derivatives targeting PITPα/β considered targets for cancer and inflammatory pathologies. Full article