Comparative Structural Analysis Research Articles

Structural basis for the transport and regulation mechanism of the Multidrug resistance-associated protein 2.

Multidrug resistance-associated protein 2 (MRP2) is an ATP-powered exporter important for maintaining liver homeostasis and a potential contributor to chemotherapeutic resistance. Deficiencies in MRP2 function are associated with Dubin-Johnson Syndrome and increased vulnerability to liver injury from cytotoxic drugs. Using cryogenic electron microscopy (cryo-EM), we determined the structures of human MRP2 in three conformational states: an autoinhibited state, a substrate-bound pre-translocation state, and an ATP-bound post-translocation state. These structures show that MRP2 functions through the classic alternating access model, driven by ATP binding and hydrolysis. Its cytosolic regulatory (R) domain serves as a selectivity gauge, wherein only sufficiently high concentrations of substrates can effectively compete with and disengage the R domain to initiate transport. Comparative structural analyses of MRP2 in complex with different substrates reveal how the transporter recognizes a diverse array of compounds, highlighting the transporter's role in multidrug resistance.

Comparative Structural Analysis of the Northern Potwar Deformed Zone and the Southern Potwar Platform Zone, NW‒Himalayas, Pakistan

Comparative Structural Analysis of the Northern Potwar Deformed Zone and the Southern Potwar Platform Zone, NW‒Himalayas, Pakistan

A comparative analysis of risk prevention policy tools and governance structures in Normandy (France) and Victoria (Australia): Assessing policies for high-risk sites

High-risk industrial sites are classified as the most dangerous sites for their risk of inducing damage in case of an accident, even if it is rare. Risk policies are one way to prevent damage while balancing other trade-offs. How can public authorities assess “risk policy systems” of high-risk sites in specific administrative regimes for an effective decision process taking into consideration different jurisdictions? This paper investigates the Normandy and Victorian risk policy system in France and Australia, respectively, based on qualitative approaches. By investigating two cases and fostering conceptual thinking, two assessment criteria are highlighted by different stakeholders to determine an effective risk policy. For instance, beyond the common focus on the efficiency and efficacy of risk policies, findings revealed the importance of “dialogue, participation, and cooperation” between actors and “adaptivity, flexibility, relevance, and coherence” of different tools and legal texts. Limitations and further work include testing and iterating on other assessment criteria to propose an adapted assessment framework for high-risk policies.

Comparative protein structural analyses of α-synuclein linked pathogenic variants reveal the role of N-terminally located critical region in Parkinson’s disease pathogenesis

Comparative protein structural analyses of α-synuclein linked pathogenic variants reveal the role of N-terminally located critical region in Parkinson’s disease pathogenesis

Computational fluid dynamics for the influence of cross-sectional configuration on the hydraulic characteristics in an oxidation ditch

Oxidation ditch (OD) as a widely used process in wastewater treatment plants (WWTPs) usually produces low-flow zones at the ditch bottom, which leads to potential sludge deposition. In response to this issue, this study optimized the rectangular cross-section of the OD by proposing a U-shaped configuration, and used the numerical simulation method (Flunet 6.3.26) to simulate the hydraulic characteristics in the OD with the two types of cross-section. Comparative analysis of the simulated flow field structure and gas-phase distributions between the rectangular and U-shaped cross-sections indicates that the “U-shaped” OD exhibits superior hydraulic characteristics, and can provide a foundation for further advancements in OD design.

Discovery, Structure, and Engineering of a cis‐Geranylfarnesyl Diphosphate Synthase

Abstractcis‐Prenyltransferases (cis‐PTs) catalyze the sequential head‐to‐tail condensation of isopentenyl diphosphate (IPP) to allylic diphosphates, producing mixed E–Z prenyl diphosphates of varying lengths; however, the specific enzymes synthesizing cis‐C25 prenyl diphosphates have not been identified. Herein, we present the discovery and characterization of a cis‐geranylfarnesyl diphosphate synthase (ScGFPPS) from Streptomyces clavuligerus. This enzyme demonstrates high catalytic proficiency in generating six distinct cis‐polyisoprenoids, including three C25 and three C20 variants. We determined the crystal structure of ScGFPPS. Additionally, we unveil the crystal structure of nerylneryl diphosphate synthase (NNPS), known for synthesizing an all‐cis‐C20 polyisoprenoid. Comparative structural analysis of ScGFPPS and NNPS has identified key differences that influence product specificity. Through site‐directed mutagenesis, we have identified eight single mutations that significantly refine the selectivity of ScGFPPS for cis‐polyisoprenoids. Our findings not only expand the functional spectrum of cis‐PTs but also provide a structural comparison strategy in cis‐PTs engineering.

Discovery, Structure, and Engineering of a cis-Geranylfarnesyl Diphosphate Synthase.

cis-Prenyltransferases (cis-PTs) catalyze the sequential head-to-tail condensation of isopentenyl diphosphate (IPP) to allylic diphosphates, producing mixed E-Z prenyl diphosphates of varying lengths; however, the specific enzymes synthesizing cis-C25 prenyl diphosphates have not been identified. Herein, we present the discovery and characterization of a cis-geranylfarnesyl diphosphate synthase (ScGFPPS) from Streptomyces clavuligerus. This enzyme demonstrates high catalytic proficiency in generating six distinct cis-polyisoprenoids, including three C25 and three C20 variants. We determined the crystal structure of ScGFPPS. Additionally, we unveil the crystal structure of nerylneryl diphosphate synthase (NNPS), known for synthesizing an all-cis-C20 polyisoprenoid. Comparative structural analysis of ScGFPPS and NNPS has identified key differences that influence product specificity. Through site-directed mutagenesis, we have identified eight single mutations that significantly refine the selectivity of ScGFPPS for cis-polyisoprenoids. Our findings not only expand the functional spectrum of cis-PTs but also provide a structural comparison strategy in cis-PTs engineering.

Genome-Wide Transcriptional Roles of KSHV Viral Interferon Regulatory Factors in Oral Epithelial Cells.

The viral interferon regulatory factors (vIRFs) of KSHV are known to dysregulate cell signaling pathways to promote viral oncogenesis and to block antiviral immune responses to facilitate infection. However, it remains unknown to what extent each vIRF plays a role in gene regulation. To address this, we performed a comparative analysis of the protein structures and gene regulation of the four vIRFs. Our structure prediction analysis revealed that despite their low amino acid sequence similarity, vIRFs exhibit high structural homology in both their DNA-binding domain (DBD) and IRF association domain. However, despite this shared structural homology, we demonstrate that each vIRF regulates a distinct set of KSHV gene promoters and human genes in epithelial cells. We also found that the DBD of vIRF1 is essential in regulating the expression of its target genes. We propose that the structurally similar vIRFs evolved to possess specialized transcriptional functions to regulate specific genes.

Tardigrade secretory proteins protect biological structures from desiccation

Tardigrades, microscopic animals that survive a broad range of environmental stresses, express a unique set of proteins termed tardigrade-specific intrinsically disordered proteins (TDPs). TDPs are often expressed at high levels in tardigrades upon desiccation, and appear to mediate stress adaptation. Here, we focus on the proteins belonging to the secreted family of tardigrade proteins termed secretory-abundant heat soluble (“SAHS”) proteins, and investigate their ability to protect diverse biological structures. Recombinantly expressed SAHS proteins prevent desiccated liposomes from fusion, and enhance desiccation tolerance of E. coli and Rhizobium tropici upon extracellular application. Molecular dynamics simulation and comparative structural analysis suggest a model by which SAHS proteins may undergo a structural transition upon desiccation, in which removal of water and solutes from a large internal cavity in SAHS proteins destabilizes the beta-sheet structure. These results highlight the potential application of SAHS proteins as stabilizing molecules for preservation of cells.

Comparative analysis of bacterial community structure and physicochemical quality in high-temperature Daqu of different colors in Qingzhou production area

To compare the effects of differences in Daqu making technology and production regions on the bacterial composition and physicochemical properties of high-temperature Daqu (HTD), this study analyzed the bacterial community structure of three colors of HTD in the Qingzhou production area and measured their physicochemical quality. At the same time, a comparative analysis was conducted on the bacterial composition of Qingzhou and Xiangyang regions. The results revealed that the HTD in the Qingzhou area exhibited a diverse bacterial community dominated by Lentibacillus, Scopulibacillus, and Staphylococcus. The black HTD displayed the lowest bacterial richness (P < 0.05) and a relatively unique microbial structure. Significant variations were observed in the physicochemical qualities of the three colors of HTD. Notably, white HTD demonstrated higher moisture and ash content, saccharification and liquor-producing power. Yellow HTD exhibited higher amino nitrogen and protein content, and black HTD displayed higher water activity, acidity, and starch content. The variation in Bacillus, Limosilactobacillus, and Weissella distributions across different colors of HTD primarily contributed to these findings. From the HTD samples in the Qingzhou area, Bacillus (61.90 %) and lactic acid bacteria (17.46 %) being the predominant cultivable communities. Cluster analysis identified significant differences in bacterial communities among HTD samples from various production areas. It can enhance the understanding of HTD quality in the Qingzhou area and offer insights for optimizing HTD and Maotai-flavor Baijiu quality.

The unique geometries and magnetic anisotropy energy of FenPt (n = 3–13) clusters: A first-principles investigation

Enthusiasm for exploring magnetic anisotropy energy (MAE) and spin–orbit coupling (SOC) effects in magnetic studies of transition metal alloy clusters remains high. In this paper, the first-principle method was used to investigate the global minimum energy structure of FenPt (n = 3–13) clusters and their interesting magnetic properties. Comparative structural analyses show that FenPt (n = 3–13) clusters have unique structures, and their relative stability analyses indicate that the increase in the number of atoms influences the geometrical arrangement of the clusters. The exploration of magnetic properties has focused on two areas. First, FenPt (n = 3–13) is found to have a large magnetic moment, while the magnetic moment increment surprisingly varies in the same way in different cases with and without the inclusion of SOC effects. Second, the calculations show that FenPt (n = 3, 4, 9, 13) has MAE, ranging from 1.420-2.687 meV/atom. The SOC matrix results show the interaction of Pt dx2-y2 and Pt dxy, and the interaction of Pt dz2 and Pt dyz, exhibit an indispensable force in determining the MAE.

Tetraanionic Oligo-Dioxaborines: Strongly Absorbing Near-Infrared Dyes.

Polymethine dyes of tetraanionic nature comprising 1,3,2-dioxaborine rings in the polymethine chain and end-groups of different electron-accepting abilities have been synthesized. They can be considered as oligomeric polymethines, where a linear conjugated π-system passes through three 1,3,2-dioxaborine units and a number of tri- and dimethine π-bridges between two end-groups. The obtained dyes exhibit near-infrared absorption and fluorescence, with molar absorption coefficients reaching as high as 564000 M-1 cm-1 in DMF, rendering them among the strongest absorbers known. The novel compounds are bright NIR fluorophores, with fluorescence quantum yields up to 0.13 in DMF. A comparative analysis of the electronic structure of the obtained dyes with respective dianionic and trianionic oligomers was conducted through quantum chemical calculations.

Supramolecular synthons in hydrates and solvates of lamotrigine: a tool for cocrystal design.

The molecule of anti-epileptic drug lamotrigine [LAM; 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine] is capable of the formation of multicomponent solids. Such an enhanced tendency is related to the diverse functionalities of the LAM chemical groups able to form hydrogen bonds. Two robust synthons are recognized in the supramolecular structure of LAM itself formed via N-H...N hydrogen bond: homosynthon, so-called aminopyridine dimer or synthon 1 [R22(8)] and larger homosynthon 2 [R32(8)]. The synthetic procedures for a new hydrate and 11 solvates of LAM (in the series: with acetone, ethanol: two polymorphs: form I and form II, 2-propanol, n-butanol, tert-butanol, n-pentanol, benzonitrile, acetonitrile, DMSO and dioxane) were performed. The comparative solid state structural analysis of a new hydrate and 11 solvates of LAM has been undertaken in order to establish robustness of the supramolecular synthons 1 and 2 found in the crystal structure of LAM itself as well as LAM susceptibility to build methodical solid state supramolecular architecture in the given competitive surrounding of potential hydrogen bonds. The aminopyridine dimer homosynthon 1 [R22(8)] has been switched from para-para (P-P) topology to ortho-ortho (O-O) topology in all crystal structures, except in LAM:n-pentanol:water solvate where it remains P-P. Homosynthon 2 [R32(8)] of the LAM crystal structure imitates in the LAM solvates as a heterosynthon by replacing the triazine nitrogen proton acceptor atoms of LAM with the proton acceptors of solvates molecules.

Interclonal variability in sensitivity to wind breakage: Comparative analysis of the mechanical behaviour of stems of two Hevea clones

The rubber tree (Hevea brasiliensis) is the main source of natural rubber production, with more than 14 million tonnes produced each year. Unfortunately, throughout their economic lifespan on the plantation (between 35 and 40 years), heveas trees are sensitive to wind damage, especially trunk breakage. Over a 30-year period, it is estimated that losses due to the wind breakage of tree stems reach nearly 40%. Industrial hevea plantations are organized in monoclonal plots. Clones are selected based on their productivity, disease resistance, etc., but not for their mechanical behaviour or sensitivity to wind-induced breakage, as breeders lack the appropriate tools to assess these criteria. Field observations highlight variations among clones in their susceptibility to wind breakage, underscoring the increased importance of evaluating mechanical criteria. Among the known causes of these differences in Hevea trees are competition between latex production and growth, crown shape and the presence of tension wood. In this article, we investigated the mechanical behaviour of the stems of two Hevea clones. One, IRCA825, is recognized as very sensitive, while the other, IRCA41, is known for its resistance to wind breakage. We measured biomechanical parameters such as trunk bending stiffness (EI), green wood stiffness (E) and modulus of rupture (MOR). To assess these parameters, we performed bending tests until breakage on standing trees of clonal fields in Ivory Coast, followed by wood characterisation tests in laboratory. A comparative analysis of the bending tests revealed that clones IRC825 and IRCA41 exhibit equivalent trunk bending stiffness. Nevertheless, IRCA41 differs from IRCA825 by having higher green wood stiffness and breaking strength, attributes that mainly explains its higher wind resistance. Comparative analysis of the wood structure indicated that the differences in wood stiffness and breaking strength are mainly attributed to the higher wood density in IRCA41 compared to IRCA825, with no discernible differences in microfibril angle and specific modulus.

Filamentation and inhibition of prokaryotic CTP synthase with ligands.

Cytidine triphosphate synthase (CTPS) plays a pivotal role in the de novo synthesis of cytidine triphosphate (CTP), a fundamental building block for RNA and DNA that is essential for life. CTPS is capable of directly binding to all four nucleotide triphosphates: adenine triphosphate, uridine triphosphate, CTP, and guanidine triphosphate. Furthermore, CTPS can form cytoophidia in vivo and metabolic filaments in vitro, undergoing regulation at multiple levels. CTPS is considered a potential therapeutic target for combating invasions or infections by viral or prokaryotic pathogens. Utilizing cryo-electron microscopy, we determined the structure of Escherichia coli CTPS (ecCTPS) filament in complex with CTP, nicotinamide adenine dinucleotide (NADH), and the covalent inhibitor 6-diazo-5-oxo- l-norleucine (DON), achieving a resolution of 2.9 Å. We constructed a phylogenetic tree based on differences in filament-forming interfaces and designed a variant to validate our hypothesis, providing an evolutionary perspective on CTPS filament formation. Our computational analysis revealed a solvent-accessible ammonia tunnel upon DON binding. Through comparative structural analysis, we discern a distinct mode of CTP binding of ecCTPS that differs from eukaryotic counterparts. Combining biochemical assays and structural analysis, we determined and validated the synergistic inhibitory effects of CTP with NADH or adenine on CTPS. Our results expand our comprehension of the diverse regulatory aspects of CTPS and lay a foundation for the design of specific inhibitors targeting prokaryotic CTPS.

Codon Usage Characteristics and Evolutionary Analysis of Mitochondrial Genome of Winter Squash (Cucurbita maxima Duch.)

Mitochondrial genomes are essential components of eukaryotic cells, understanding their structural characteristics and codon usage bias is critical. Winter squash (Cucurbita maxima Duch ex Poiret) is an economically important cucurbit crop. To clarify its structural characteristics and codon usage bias of mitochondrial genome, as well as the evolutionary characteristics in the Cucurbitaceae family, whole genome sequencing analysis of C. maxima mitochondrial genome was carried out. The results revealed that the total length of the C. maxima mitochondrial genome was 640,814 bp, containing 9,162,318,300 bp of bases. There were 68 annotated genes identified. The mitochondrial coding genes of C. maxima exhibited an average GCall content of 42.57%, with the last position enriched in A/T bases. Codon usage analysis indicated weak codon bias, with the effective codon number (ENC) ranging from 44.22 to 61.00. Correlation analysis and neutrality plot analysis demonstrated a nonsignificant correlation between GC3 and GC12. PR2-plot and ENC-plot analysis further supported the influence of natural selection on the codon preference in the C. maxima mitochondrial genome. Relative synonymous codon usage (RSCU) analysis identified 19 optimal codons, with a preference for U or A as the final base. The analysis of scattered repeat sequences in the genome indicated a high frequency of forward and palindromic repeats in the C. maxima mitochondrial genome. Nucleic acid diversity analysis highlighted rpl5 as the gene with the highest variability. Comparative analysis of mitochondrial structure and phylogenetic tree analysis revealed a close evolutionary relationship between C. maxima and Cucurbita pepo, showing synteny in evolution. Homologous fragment analysis demonstrated a similarity of over 70% between the C. maxima mitochondrial genome and chloroplast genome fragments. These findings provide a foundation for C. maxima identification and phylogenetic studies.

유형론적 관점에서 본 중한 병렬구조 비교연구

Parallelism means that two grammatical units are connected in an equal relationship, and is a linguistic structure that universally exists among the world's languages. However, because the realization method of the parallel structure is different for each language, this paper conducted a comparative analysis of the parallel structure of Korean and Chinese, especially parallel phrases, from a typological perspective to examine the commonalities and differences as well as the causes. This can be summarized as follows: The Chinese-Korean parallel structure can be divided into several types depending on the classification criteria. Based on the semantic type, it can be broadly classified into 'equal type', 'transitional type', and 'selective type', and depending on the part of speech of the parallel item, 'name-name parallel structure', 'dong-dong parallel structure', and 'type- It was confirmed that it can be divided into a ‘parallel structure’. In addition, this paper examined the syntactic function of the Chinese-Korean parallel structure in four aspects, including the degree of marking of the Chinese-Korean parallel structure, the syntactic position distribution of the parallel structure, the position of the conjunction, and whether heterogeneous parallelism is possible. In addition, the similarities and differences between Korean and Chinese parallel structures were explained in connection with the language types of Chinese and Korean and the theory of linguistic typology.

Comparative analysis of the crystal structures of hydrates and sodium salts of monensin and its new C-26 succinate ester

Monensin succinate ester hydrate (2-H2O) has been synthesized by the succinylation of C-26 hydroxyl group of monensin (1) using a simple reaction with succinic anhydride. Additionally, the sodium salt (2-Na) of monensin succinate ester has been obtained. Molecular structures of both compounds (2-H2O and 2-Na) were studied using X-ray diffraction of single crystals and spectroscopic methods. According the crystallographic studies of 2-H2O and 2-Na, the molecules are held together as dimers linked by the centrosymmetric pairs of intermolecular hydrogen bonds between the carboxylic groups. The crystal structures of compounds 2-H2O and 2-Na are compared to those of the known monensin acid hydrate (1-H2O) and 1:1 inclusion complex of monensin A sodium salt with acetonitrile (1-Na-CH3CN) and that of newly obtained monensin sodium salt monohydrate (1-Na-H2O). Comparison of these structures showed a significant impact of C-26 succinate ester moiety on the coordination of the Na+ cation and hydrogen bond.

Comparative chloroplast genomes of Dactylicapnos species: insights into phylogenetic relationships

BackgroundDactylicapnos is a climbing herbaceous vine, distributed from the Himalayas to southwestern China, and some of the species have important medicinal values. However, the chloroplast genomes of Dactylicapnos have never been investigated. In this study, chloroplast genomes of seven Dactylicapnos species covering all three sections and one informal group of Dactylicapnos were sequenced and assembled, and the detailed comparative analyses of the chloroplast genome structure were provided for the first time.ResultsThe results showed that the chloroplast genomes of Dactylicapnos have a typical quadripartite structure with lengths from 172,344 bp to 176,370 bp, encoding a total of 133–140 genes, containing 88–94 protein-coding genes, 8 rRNAs and 37–39 tRNAs. 31 codons were identified as relative synonymous codon usage values greater than one in the chloroplast genome of Dactylicapnos genus based on 80 protein-coding genes. The results of the phylogenetic analysis showed that seven Dactylicapnos species can be divided into three main categories. Phylogenetic analysis revealed that seven species form three major clades which should be treated as three sections.ConclusionsThis study provides the initial report of the chloroplast genomes of Dactylicapnos, their structural variation, comparative genomic and phylogenetic analysis for the first time. The results provide important genetic information for development of medical resources, species identification, infrageneric classification and diversification of Dactylicapnos.

Comparative analysis of the community structure of macroinvertebrates in reservoir and river ecosystems in Jinan

The benthic fauna of the Jinan reservoir ecosystem and river ecosystem is dominated by Insecta species, followed by Gastropoda species, and the species of Insecta and Gastropoda are more in rivers than in reservoirs. Judging from the seasonal changes of benthic species in the two ecosystems, both showed a trend of high in spring and low in autumn. Judging from the changes in the density of benthic invertebrate in the water bodies of the two ecosystems, the total density of benthic invertebrate in the water bodies of the reservoir is low, and the monthly density changes are small, the total density of benthic invertebrate in the river ecosystem is higher than that in the reservoir ecosystem, and the density fluctuation is relatively large. The fluctuation range of benthic diversity in the reservoir ecosystem is smaller than that in the river ecosystem.