Structure-function Relationships Research Articles

Quantitative assessment of the nanoanatomy of the contractile vacuole complex in Trypanosoma cruzi.

Trypanosoma cruzi uses various mechanisms to cope with osmotic fluctuations during infection, including the remodeling of organelles such as the contractile vacuole complex (CVC). Little is known about the morphological changes of the CVC during pulsation cycles occurring upon osmotic stress. Here, we investigated the structure-function relationship between the CVC and the flagellar pocket domain where fluid discharge takes place-the adhesion plaque-during the CVC pulsation cycle. Using TcrPDEC2 and TcVps34 overexpressing mutants, known to have low and high efficiency for osmotic responses, we described a structural phenotype for the CVC that matches their corresponding physiological responses. Quantitative tomography provided data on the volume of the CVC and spongiome connections. Changes in the adhesion plaque during the pulsation cycle were also quantified and a dense filamentous network was observed. Together, the results suggest that the adhesion plaque mediates fluid discharge from the central vacuole, revealing new aspects of the osmoregulatory system in T. cruzi.

Actin cytoskeleton and associated myosin motors within the renal epithelium.

This review highlights the complexity of renal epithelial cell membrane architectures and organelles through careful review of ultrastructural and physiological studies published over the past several decades. We also showcase the vital roles played by the actin cytoskeleton and actin-associated myosin motor proteins in regulating cell type-specific physiological functions within the cells of the renal epithelium. The purpose of this review is to provide a fresh conceptual framework to explain the structure-function relationships that exist between the actin cytoskeleton, organelle structure, and cargo transport within the mammalian kidney. With recent advances in technologies to visualize the actin cytoskeleton and associated proteins within intact kidneys, it has become increasingly imperative to reimagine the functional roles of these proteins in situ to provide a rationale for their unique, cell type-specific functions that are necessary to establish and maintain complex physiological processes.

Genomics 2 Proteins portal: a resource and discovery tool for linking genetic screening outputs to protein sequences and structures.

Recent advances in AI-based methods have revolutionized the field of structural biology. Concomitantly, high-throughput sequencing and functional genomics have generated genetic variants at an unprecedented scale. However, efficient tools and resources are needed to link disparate data types-to 'map' variants onto protein structures, to better understand how the variation causes disease, and thereby design therapeutics. Here we present the Genomics 2 Proteins portal ( https://g2p.broadinstitute.org/ ): a human proteome-wide resource that maps 20,076,998 genetic variants onto 42,413 protein sequences and 77,923 structures, with a comprehensive set of structural and functional features. Additionally, the Genomics 2 Proteins portal allows users to interactively upload protein residue-wise annotations (for example, variants and scores) as well as the protein structure beyond databases to establish the connection between genomics to proteins. The portal serves as an easy-to-use discovery tool for researchers and scientists to hypothesize the structure-function relationship between natural or synthetic variations and their molecular phenotypes.

Precisely Constructing Molecular Junctions in Hydrogen-Bonded Organic Frameworks for Efficient Artificial Photosynthetic CO2 Reduction.

The development of artificial photocatalysts to convert CO2 into renewable fuels and H2O into O2 is a complex and crucial task in the field of photosynthesis research. The current challenge is to enhance photogenerated charge separation, as well as to increase the oxidation capability of materials. Herein, a molecular junction-type porphyrin-based crystalline photocatalyst (Ni-TCPP-TPyP) was successfully self-assembled by incorporating a nickel porphyrin complex as a reduction site and pyridyl porphyrin as an oxidation site via hydrogen bonding and π-π stacking interactions. The resulting material has a highly crystalline structure, and the formation of inherent molecular junctions can accelerate photogenerated charge separation and transport. Thus, Ni-TCPP-TPyP achieved an excellent CO production rate of 309.3 μmol g-1 h-1 (selectivity, ~100%) without the use of any sacrificial agents, which is more than ten times greater than that of single-component photocatalyst (Ni-TCPP) and greater than that of the most organic photocatalysts. The structure-function relationship was investigated by femtosecond transient absorption spectroscopy and density functional theory calculations. Our work provides new insight for designing efficient artificial photocatalysts, paving the way for the development of clean and renewable fuels through the conversion of CO2 using solar energy.

Photocurable Hypervalent Fluorinated Sulfur Containing Thin Films with Remarkable Hardness and Modulus

Novel tetrafluoro-λ6-sulfanyl-containing oligomers prepared by visible light-promoted addition of 1,4-(bis-chlorotetrafluoro-λ6-sulfanyl) benzene or 1,3-(bis-chlorotetrafluoro-λ6-sulfanyl) benzene to either 1,4-diethynyl benzene or the 1,3-diethynyl isomers form hard, stress resistant thin films on spin casting. The isomeric oligomers were utilized to establish a structure-function relationship for the mechanical properties of films prepared from the oligomers. The Young’s moduli of 145-nm-thick cured films could reach 60 GPa. The measured hardnesses, between 1.57 and 2.77 GPa, were more than double those of polymethyl methacrylate (PMMA) films. Curing of the tetrafluoro-λ6-sulfanyl-containing polymer films by UV irradiation resulted in coatings that exhibited remarkable hardness and modulus with good surface adhesion to silicon.

Conformational Selection in Enzyme-Catalyzed Depolymerization of Bio-based Polyesters.

Enzymatic degradation of polymers holds promise for advancing towards a bio-based economy. However, bulky polymers presents challenges in accessibility for biocatalysts, hindering depolymerization reactions. Beyond the impact of crystallinity, polymer chains can reside in different conformations affecting binding efficiency to the enzyme. We previously showed that the gauche and trans chain conformers associated with crystalline and amorphous regions of the synthetic polyethylene terephthalate (PET) display different affinity to PETase, thus affecting the depolymerization rate. However, structural-function relationships for biopolymers remain poorly understood in biocatalysis. In this study, we explored biodegradation of by-us previously synthesized bio-polyesters made from a rigid bicyclic chiral terpene-based diol and copolymerized with various renewable diesters. Herein, four of those polyesters spanning from semi-aromatic to aliphatic were subjected to enzymatic degradations in concert with induced-fit docking (IFD) analyses. Our findings demonstrate the importance of conformational selection in enzymatic depolymerization of biopolymers. A straight or twisted conformation of the polymer chain is crucial in biocatalytic degradation by showing different affinities to enzyme ground-state conformers. This work highlights the importance of considering the conformational match between the polymer and the enzyme to optimize the biocatalytic degradation efficiency of biopolymers, providing valuable insights for the development of sustainable bioprocesses.

Lactonization of Diols Over Highly Efficient Metal-Based Catalysts.

Lactones has gained increasing attention in recent years due to wide application in polymer and pharmaceutical industries. Traditional synthetic methods of lactones often involve harsh operating temperature, use of strong alkalis and toxic oxidants. Therefore, lactonization of diols under milder conditions have been viewed as the most promising route for future commercialization. A variety of metal catalysts (Ru, Pt, Ir, Au, Fe, Cu, Co, and Zn) have been developed for highly efficient oxidant-, acceptor-, base- and additive-free lactonization processes. However, only a few initial attempts have been reported with no further details on catalytic mechanism being disclosed in literature. There demands a systematic study of the mechanistic details and the structure-function relationship to guide the catalyst design. In this work, we critically reviewed and discussed the structure-function relationship, the catalytic reaction mechanism, the catalyst stability, as well as the effect of oxidant and solvent for lactonization of diols. This work may provide additional insights for the development of other oxygen-containing functional molecules for material science and technologies.

Autoclaved Starch: Structure and Functionality Relationship in a Matrix With the Same Contribution ofAmylose and Amylopectin.

The rational use of autoclaved starches in food applications is difficult because there is a lack of information on their structure-functionality relationship. The novelty of this research relies on disclosing such an association. Hylon V starch was autoclaved at 105, 120, and 135°C to investigate its crystalline and double-helical features and its relationship with functionality. In autoclaved Hylon V starch, interactions of amylopectin and amylose improved while the crystalline regions decreased. The degree of double helices (DD) decreased after autoclaving at 105°C and the degree of order (DO) increased after treatment at 120 and 135°C. The water solubility index (WSI) (4.63-6.38%) and swelling power (SP) (4.39-7.1 g/g) increased when the temperature increased. On the other hand, water (103.49-225.01%) and oil (61.91-94.53%) holding capacity (WHC and OHC, respectively) increased after autoclaving treatment, although the values decreased with the treatment intensity. The functional properties were affected when the structure changed as a function of the treatment temperatures. PCA analysis showed that WSI and SP of autoclaved Hylon V starch were associated with a high DD, with better compaction, and with stronger amylopectin-amylose interactions. WHC and OHC were associated with better crystallinity, stronger interactions of amylopectin and amylose, and heterogeneous double-helical crystallites. These findings are useful for understanding the structure-functionality relationship of autoclaved Hylon V starch and pave the way for future research regarding the effects of its incorporation on the properties of food matrices such as bread, yogurt, cakes, and pudding.

Acceptor Subsite Mutants of Limosilactobacillus fermentum NCC 2970 GtfB 4,3-α-Glucanotransferase Regulate the Ratio of (α1 → 3)/(α1 → 6) Linkages in Biosynthesized α-Glucans.

Limosilactobacillus fermentum NCC 2970 GtfB (Lf2970 GtfB) is the only characterized 4,3-α-glucanotransferase (4,3-α-GTase) in the glycoside hydrolase (GH) 70 family belonging to the GtfB subfamily. However, the mechanism for its (α1 → 3) linkage formation remains unclear, and the structural determinants of its linkage specificity remain to be explored. Here, sequence alignment and structural comparison were conducted to identify key amino acids that may be critical for linkage specificity. Five residues of Lf2970 GtfB (D991, G1028, A1398, T1400, and E1405), located at donor and acceptor subsites, were selected for mutation. Product structure analysis revealed that D991 and G1028, located near the acceptor binding subsites, played crucial roles in linkage formation. Besides native (α1 → 4) and (α1 → 3) linkages, mutants G1028R and D991N showed 8 and 10% (α1 → 6) linkage increases compared to 1% for wild-type in products. Additionally, molecular docking studies demonstrated that the orientation of acceptor binding in G1028R and D991N mutants was favorable for (α1 → 6) linkage synthesis. However, the mutation at positions A1398, T1400, and E1405 indicated that the donor subsites contribute less to the linkage specificity. These results shed light on the structural determinants of linkage specificity of 4,3-α-GTase Lf2970 GtfB and provided insights into the structure-function relationship of family GH70.

Functional carbon nanodots enhance tomato tolerance to zinc deficient soils: Mechanisms and structure-function relationships

Zinc (Zn) deficiency is a global problem disorder affecting both crops and humans. Herein, modified functional carbon nanodots (MFCNs) with various structures and characteristics were developed to regulate tomato yields and Zn migration in plant–soil systems affected by Zn deficiency through structure–function relationships. Sulfur-doped FCNs (S-FCNs), nitrogen-doped FCNs (N-FCNs), and nitrogen‑sulfur co-doped FCNs (N,S-FCNs) were hydrothermally modified using FCNs as precursors. Their regulatory effects on tomatoes growing in Zn-deficient alkaline soils were studied in pot culture experiments. Specifically, 8 mg kg−1 of FCNs and S-FCNs improved tomato yields by 132 % and 108 %, respectively, compared with the control. However, N-FCNs and N,S-FCNs showed no significant effect on yield compared with the control (P < 0.05). Moreover, the application of FCNs or S-FCNs significantly improved fruit quality and nutritional value, including Zn content (by 26.3 % and 22.0 %, respectively) and naturally occurring antioxidants (by 3.37- and 2.08-fold for lycopene, 1.31- and 1.18-fold for flavonoids, and 2.28- and 1.89-fold for phenolics, respectively; P < 0.05). Although N-FCNs and N,S-FCNs increased Zn contents, they inhibited the synthesis of naturally occurring antioxidants in fruits. Zn bioaccessibility, uptake, and transportation in plant-soil systems were regulated by MFCNs through both direct and indirect mechanisms, including ionic reactions, plant physiology, and environmental effects. MFCNs regulated plant tolerance to Zn deficiency not only by affecting root activity, redox homeostasis, micronutrient balance, chelator synthesis, genetic expression, and plant photosynthesis but also by influencing rhizosphere soil properties and the microbial environment. Based on their dual role as “plant growth regulators” and “soil conditioners”, MFCNs may have general applicability in agriculture. This study highlights the behavior of MFCNs in plant-soil systems, providing innovative nanotools for enhancing Zn availability, crop stress resistance and environmental preservation in sustainable agriculture.

In vitro Antileishmanial Activity and In Silico Molecular Modeling Studies of Novel Analogs of Dermaseptins S4 and B2.

Leishmaniasis is responsible for approximately 65,000 annual deaths. Various Leishmania species are the predominant cause of visceral, cutaneous, or mucocutaneous leishmaniasis, affecting millions worldwide. The lack of a vaccine, emergence of resistance, and undesirable side effects caused by antileishmanial medications have prompted researchers to look for novel therapeutic approaches to treat this disease. Antimicrobial peptides (AMPs) offer an alternative for promoting the discovery of new drugs. In this study, we detail the synthesis process and investigate the antileishmanial activity against Leishmania (Viannia) braziliensis for peptides belonging to the dermaseptin (DS) family and their synthetic analogs. The MTT assay was performed to investigate the cytotoxicity of these peptides on the murine macrophage cell line RAW 264.7. Subsequently, we performed molecular modeling analysis to explore the structure-function correlation of the derivatives interacting with the parasitic membrane. All examined derivatives displayed concentration-dependent antileishmanial effect at low concentrations. Their effectiveness varied according to the peptide's proprieties. Notably, peptides with higher levels of charge demonstrated the most pronounced activities. Cytotoxicity assays showed that all the tested peptides were not cytotoxic compared to the tested conventional drug. The structure-function relationships demonstrated that the charged N-terminus could be responsible for the antileishmanial effect observed on promastigotes. Collectively, these results propose that dermaseptins (DS) might offer potential as promising candidates for the development of effective antileishmanial therapies.

Understanding the effects of mineralization and structure on the mechanical properties of tendon-bone insertion using mesoscale computational modeling

Tendon-bone fibrocartilaginous insertion, or enthesis, is a specialized interfacial region that connects tendon and bone, effectively transferring forces while minimizing stress concentrations. Previous studies have shown that insertion features gradient mineralization and branching fiber structure, which are believed to play critical roles in its excellent function. However, the specific structure-function relationship, particularly the effects of mineralization and structure at the mesoscale fiber level on the properties and function of insertion, remains poorly understood. In this study, we develop mesoscale computational models of the distinct fiber organization at tendon-bone insertions, capturing the branching network from tendon to interface fibers and the different mineralization scales. We specifically analyze three key descriptors: the mineralization scale of interface fibers, the mean, and relative standard deviation of the local branching angles of interface fibers. Tensile test simulations on insertion models with varying mineralization scales of interface fibers and structures are performed to mimic the primary loading condition applied to the insertion. We measure and analyze five representative mechanical properties: Young's modulus, strength, toughness, resilience, and failure strain. Our results reveal that mechanical properties are significantly influenced by the three key descriptors, with tradeoffs observed between mutually exclusive properties. For instance, strength and resilience plateau beyond a certain mineralization scale, while failure strain and Young's modulus exhibit monotonic decreasing and increasing trends, respectively. Consequently, there exists an optimal mineralization scale for toughness due to these tradeoffs. By analyzing the mesoscale deformation and failure mechanisms from simulation trajectories, we identify three fracture regimes closely related to the trends in mechanical properties, supporting the observed tradeoffs. Additionally, we examine in detail the effects of the mean and relative standard deviation of local branching angles on mechanical properties and deformation mechanisms. Overall, our study enhances the fundamental understanding of the composition-structure-function relationships at the tendon-bone insertion, complementing recent experimental studies. The mechanical insights from our work have the potential to guide the future biomimetic design of fibrillar adhesives and interfaces for joining soft and hard materials.

Associating structural characteristics to immunomodulating properties of carrot rhamnogalacturonan-I fractions

Carrot rhamnogalacturonan-I (cRG-I) is a polydisperse polysaccharide with molecular weights of 7–250 kDa. Using size exclusion chromatography cRG-I was fractionated and pooled in fractions (PF1–6). All fractions contained the same RG-I monosaccharides and similar glycosidic linkages although in varying relative amounts. The main differences were in rhamnose substitution, arabinan- and galactan side chain length and in levels of acetylation and methyl esterification. Atomic force microscopy showed either spheric or elongated structures for cRG-I and its derived fractions. To gain insight in the structure-function relationship of cRG-I, the immunomodulatory effect of the six fractions and their saponified derivatives was assessed in vitro. All fractions, except PF2, dose-dependently stimulated TNFα, IL-6, IL-1β, IL-8 and IL-10 production in peripheral blood mononuclear cells (PBMCs) of three healthy donors. Cytokine levels were largely influenced by the Mw and degree of esterification of the individual fractions. Notably, the highest Mw fraction (100 kDa) displayed the most potent activity, which was strongly reduced after the removal of ester residues by saponification. In contrast, the 75 kDa Mw population (PF2) proved inactive while its saponified counterpart exhibited substantial immunomodulatory activity. This confirmed the role of ester residues on the immune profile of RG-I subpopulations.

Hand-jaw coordination as mice handle food is organized around intrinsic structure-function relationships.

Rodent jaws evolved structurally to support dual functionality, for either biting or chewing food. Rodent hands also function dually during food handling, for actively manipulating or statically holding food. How are these oral and manual functions coordinated? We combined electrophysiological recording of muscle activity and kilohertz kinematic tracking to analyze masseter and hand actions as mice of both sexes handled food. Masseter activity was organized into two modes synchronized to hand movement modes. In holding/chewing mode, mastication occurred as rhythmic (∼5 Hz) masseter activity while the hands held food below the mouth. In oromanual/ingestion mode, bites occurred as lower-amplitude aperiodic masseter events that were precisely timed to follow regrips (by ∼200 ms). Thus, jaw and hand movements are flexibly coordinated during food handling: uncoupled in holding/chewing mode, and tightly coordinated in oromanual/ingestion mode as regrip-bite sequences. Key features of this coordination were captured in a simple model of hierarchically orchestrated mode-switching and intra-mode action sequencing. We serendipitously detected an additional masseter-related action, tooth-sharpening, identified as bouts of higher-frequency (∼13 Hz) rhythmic masseter activity, which was accompanied by eye displacement, including rhythmic proptosis, attributable to masseter contractions. Collectively, the findings demonstrate how a natural, complex, and goal-oriented activity is organized as an assemblage of distinct modes and complex actions, adapted for the divisions of function arising from anatomical structure. These results reveal intricate, high-speed coordination of disparate effectors, and show how natural forms of dexterity can serve as a model for understanding the behavioral neurobiology of multi-body-part coordination in general.Significance statement Survival hinges on efficiently handling and ingesting food. During food handling, mice switch between statically holding and actively manipulating food with the hands, and also between biting with the incisors or chewing with the molars. Using masseter electromyography and kilohertz frame rate video, we show that the two modes of hand movement and of jaw movement are tightly linked, with holding co-occurring with chewing and handling with biting. On faster timescales, biting is precisely timed to occur after rapid sequences of manipulative hand movements. Our findings reveal fast, intricate, hierarchical coordination of hand and jaw movements, show how morphology influences the organization of complex behavior, and establish food handling as a model for neurobiological studies of multi-body-part coordination.

Bifunctional ArsI Dioxygenase from Acidovorax sp. ST3 with Both Methylarsenite [MAs(III)] Demethylation and MAs(III) Oxidation Activities.

Methylated arsenicals, including highly toxic species, such as methylarsenite [MAs(III)], are pervasive in the environment. Certain microorganisms possess the ability to detoxify MAs(III) by ArsI-catalyzed demethylation. Here, we characterize a bifunctional enzyme encoded by the arsI gene from Acidovorax sp. ST3, which can detoxify MAs(III) through both the demethylation and oxidation pathways. Deletion of the 22 C-terminal amino acids of ArsI increased its demethylation activity while reducing the oxidation activity. Further deletion of 44 C-terminal residues enhanced the MAs(III) demethylation activity. ArsI has four vicinal cysteine pairs, with the first pair being necessary for MAs(III) demethylation, while at least one of the other three pairs contributes to MAs(III) oxidation. Molecular modeling and site-directed mutagenesis indicated that one of the C-terminal vicinal cysteine pairs is involved in modulating the switch between oxidase and demethylase activity. These findings underscore the critical role of the C-terminal region in modulating the enzymatic activities of ArsI, particularly in MAs(III) demethylation. This research reveals the structure-function relationship of the ArsI enzyme and advances our understanding of the MAs(III) metabolism in bacteria.

Structure, Properties and Degradation of Self-Assembled Fibrinogen Nanofiber Scaffolds.

Self-assembled fibrinogen nanofibers are promising candidates for skin tissue engineering due to their biocompatibility and ability to mimic the native blood clot architecture. Here, we studied the structure-property relationship and degradation of rehydrated fibrinogen nanofibers prepared by salt-induced self-assembly, focusing on the effect of scaffold layering, cross-linking time and freeze-drying. Optimal fiber stability was achieved with cross-linking by formaldehyde (FA) vapor, while treatment with liquid aldehydes, genipin, EDC, and transglutaminase failed to preserve the nanofibrous architecture upon rehydration. Scaffold layering did not significantly influence the mechanical properties but changed the scaffold architecture, with bulk fiber scaffolds being more compact than layered scaffolds. Freeze-drying maintained the mechanical properties and interconnected pore network with average pore diameters around 20 μm, which will enhance the storage stability of self-assembled fibrinogen scaffolds. Varying cross-linking times altered the scaffold mechanics without affecting the swelling behavior, indicating that scaffold hydration can be controlled independently of the mechanical characteristics. Cross-linking times of 240 min increased scaffold stiffness and decreased elongation, while 30 min resulted in mechanical properties similar to native skin. Cross-linking for 120 min was found to reduce scaffold degradation by various enzymes in comparison to 60 min. Overall, after 35 days of incubation, plasmin and a combination of urokinase and plasminogen exhibited the strongest degradative effect, with nanofibers being more susceptible to enzymatic degradation than planar fibrinogen due to their higher specific surface area. Based on these results, self-assembled fibrinogen fiber scaffolds show great potential for future applications in soft tissue engineering that require controlled structure-function relationships and degradation characteristics.

Enzymatic Synthesis of Disialyllacto-N-Tetraose (DSLNT) and Related Human Milk Oligosaccharides Reveals Broad Siglec Recognition to the Atypical Neu5Acα2-6GlcNAc Motif.

Sialic acids (Sias) are ubiquitously expressed on all types of glycans, typically as terminating residues. They usually link to galactose, N-acetylgalactosamine, or other Sia residues, forming ligands of many glycan-binding proteins. An atypical linkage to the C6 of N-acetylglucosamine (GlcNAc) has been identified in human milk oligosaccharides (HMOs, e.g., DSLNT) and tumor-associated glycoconjugates. Herein, we achieved the systematic synthesis of these HMOs in an enzymatic modular manner. The synthetic strategy relies on a novel activity of ST6GalNAc6 for efficient construction of the Neu5Acα2-6GlcNAc linkage, and another 12 specific enzyme modules for sequential HMO assembly. The structures enabled comprehensive exploration into their structure-function relationships using glycan microarray, revealing broad yet distinct recognitions by Siglecs to the atypical Neu5Acα2-6GlcNAc motif. The work provides tools and new insights for functional study and potential applications of Siglecs and HMOs.

Achieving High-Capacity Cathode Presodiation Agent Via Triggering Anionic Oxidation Activity in Sodium Oxide.

Compensating for the irreversible loss of limited active sodium (Na) is crucial for enhancing the energy density of practical sodium-ion batteries (SIBs) full-cell, especially when employing hard carbon anode with initially lower coulombic efficiency. Introducing sacrificial cathode presodiation agents, particularly those that own potential anionic oxidation activity with a high theoretical capacity, can provide additional sodium sources for compensating Na loss. Herein, Ni atoms are precisely implanted at the Na sites within Na2O framework, obtaining a (Na0.89Ni0.05□0.06)2O (Ni-Na2O) presodiation agent. The synergistic interaction between Na vacancies and Ni catalyst effectively tunes the band structure, forming moderate Ni-O covalent bonds, activating the oxidation activity of oxygen anion, reducing the decomposition overpotential to 2.8V (vs Na/Na+), and achieving a high presodiation capacity of 710 mAh/g≈Na2O (Na2O decomposition rate >80%). Incorporating currently-modified presodiation agent with Na3V2(PO4)3 and Na2/3Ni2/3Mn1/3O2 cathodes, the energy density of corresponding Na-ion full-cells presents an essential improvement of 23.9% and 19.3%, respectively. Further, not limited to Ni-Na2O, the structure-function relationship between the anionic oxidation mechanism and electrode-electrolyte interface fabrication is revealed as a paradigm for the development of sacrificial cathode presodiation agent.

Decoding coffee cardiometabolic potential: Chemical composition, nutritional, and health relationships.

Coffee is one of the most consumed beverages worldwide, recognized for its unique taste and aroma and for its social and health impacts. Coffee contains a plethora of nutritional and bioactive components, whose content can vary depending on their origin, processing, and extraction methods. Gathered evidence in literature shows that the regular coffee consumption containing functional compounds (e.g., polysaccharides, phenolic compounds, and melanoidins) can have potential beneficial effects on cardiometabolic risk factors such as abdominal adiposity, hyperglycemia, and lipogenesis. On the other hand, coffee compounds, such as caffeine, diterpenes, and advanced glycation end products, may be considered a risk for cardiometabolic health. The present comprehensive review provides up-to-date knowledge on the structure-function relationships between different chemical compounds present in coffee, one of the most prevalent beverages present in human diet, and cardiometabolic health.

Channel Engineering of a Glutamate Exporter.

Mechanosensitive channel MscCG2 is involved in glutamate excretion in most C. glutamicum strains. Improving the excretion efficiency of MscCG2 is beneficial to the production of glutamate. In this study, structure-based rational design was carried out to obtain an improved efflux ability of exporter MscCG2 and its mechanistic advance via two strategies: widening the channel entrance for smoother entry of glutamate and reducing the electronegativity at the entrance of the channels to minimize the rejection of negatively charged glutamate entry. The designed variants were found to enhance glutamate excretion by 2 to 3.3-fold in the early phase and 1.1-fold to 1.5-fold in the late phase of fermentation. The enhanced glutamate excretion was further confirmed by using glutamate toxic analog 4-fluoroglutamate (4-FG) and Glu-Glu peptide uptake and glutamate export assay. Molecular dynamic (MD) simulations revealed that the amino acid substitutions indeed enlarged the channel entrance and reduced the repulsion of glutamate when entering the channel. The finding of this study is important for understanding the underlying structure-function relationship and the mechanism of glutamate secretion to improve glutamate efflux efficiency of glutamate exporter.