Relational structure-aware knowledge graph representation in complex space

Relations in knowledge graphs have rich relational structures and various binary relational patterns. Various relation modelling strategies are proposed for embedding knowledge graphs, but they fail to fully capture both features of relations, rich relational structures and various binary relational patterns. To address the problem of insufficient embedding due to the complexity of the relations, we propose a novel knowledge graph representation model in complex space, namely MARS, to exploit complex relations to embed knowledge graphs. MARS takes the mechanisms of complex numbers and message-passing and then embeds triplets into relation-specific complex hyperplanes. Thus, MARS can well preserve various relation patterns, as well as structural information in knowledge graphs. In addition, we find that the scores generated from the score function approximate a Gaussian distribution. The scores in the tail cannot effectively represent triplets. To address this particular issue and improve the precision of embeddings, we use the standard deviation to limit the dispersion of the score distribution, resulting in more accurate embeddings of triplets. Comprehensive experiments on multiple benchmarks demonstrate that our model significantly outperforms existing state-of-the-art models for link prediction and triple classification. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Preferential Hydrolysis of Aberrant Intermediates by the Type II Thioesterase in Escherichia coli Nonribosomal Enterobactin Synthesis: Substrate Specificities and Mutagenic Studies on the Active-Site Residues

The type II thioesterase EntH is a hotdog fold protein required for optimal nonribosomal biosynthesis of enterobactin in Escherichia coli. Its proposed proofreading activity in the biosynthesis is confirmed by its efficient restoration of enterobactin synthesis blocked in vitro by analogs of the cognate precursor 2,3-dihydroxybenzoate. Steady-state kinetic studies show that EntH recognizes the phosphopantetheine group and the pattern of hydroxylation in the aryl moiety of its thioester substrates. Remarkably, it is able to distinguish aberrant intermediates from the normal one in the enterobactin assembly line by demonstrating at least 10-fold higher catalytic efficiency toward thioesters derived from aberrant aryl precursors without a para-hydroxyl group, such as salicylate. By structural comparison and site-directed mutagenesis, the thioesterase is found to possess an active site closely resembling that of the 4-hydroxybenzoyi-CoA thioesterase from Arthrobacter sp. strain SU and to involve an acidic residue (glutamate-63) as the catalytic base or nucleophile like all other hotdog thioesterases. In addition, the EntH specificities toward the substrate hydroxylation pattern are found to depend on the active-site histidine-54, threonine-64, serine-67, and methionine-68 with the selectivity significantly reduced or even reversed when they are individually replaced by alanine. These residues are likely responsible for differential interaction of the enzyme with the substrates which leads to distinction between the normal and aberrant precursors in the enterobactin assembly line. These results show that the type II thioesterase evolves its distinctive ability to recognize the aberrant intermediates from the versatile catalytic platform of hotdog proteins and suggests an active search mechanism for type 11 thioesterases in nonribosomal peptide synthesis

A Model Tree-Based Vehicle Emission Model at Freeway Toll Plazas

With the increased concern over sustainable development, many efforts have been made to alleviate air quality deterioration. Freeway toll plazas can cause serious pollution, due to the increased emissions caused by stop-and-go operations. Different toll collections and different fuel types obviously influence the vehicle emissions at freeway toll plazas. Therefore, this paper proposes a model tree-based vehicle emission model by considering these factors. On-road emissions data and vehicle operation data were obtained from two different freeway toll plazas. The statistical analysis indicates that different methods of toll collection and fuel types have significant impacts on vehicle emissions at freeway toll plazas. The performance of the proposed model was compared with a polynomial regression method. Based on the results, the mean absolute percentage error (MAPE), root mean squared error (RMSE), and mean absolute error (MAE) of the proposed model were all smaller, while the R-squared value increased from 0.714 to 0.833. Finally, the variations of vehicle emissions at different locations of freeway toll plazas were calculated and shown in heat maps. The results of this study can help better estimate the vehicle emissions and give advice to the development of electronic toll collection (ETC) lanes and relevant policies at freeway toll plazas

Molecular basis of the general base catalysis of an α/β-hydrolase catalytic triad

Background: The α/β-hydrolase MenH uses its Ser-His-Asp triad as a specific general basis with a poorly understood mechanism. Results: An open-closed conformational change is identified in the enzyme catalysis. Conclusion: The conformational change controls the formation and reactivity of the catalytic triad. Significance: The catalytic versatility of the Ser-His-Asp triad is expanded by the open-closed structural change

Stabilization of the Second Oxyanion Intermediate by 1,4-Dihydroxy-2-naphthoyl-Coenzyme A Synthase of the Menaquinone Pathway: Spectroscopic Evidence of the Involvement of a Conserved Aspartic Acid

1,4-Dihydroxy-2-naphthoyl-coenzyme A (DHNA-CoA) synthase, or MenB, catalyzes an intramolecular Claisen condensation involving two oxyanion intermediates in the biosynthetic pathway of menaquinone, an essential respiration electron transporter in many microorganisms. Here we report the finding that the DHNA-CoA product and its analogues bind and inhibit the synthase from Escherichia coli with significant ultraviolet-visible spectral changes, which are similar to the changes induced by deprotonation of the free inhibitors in a basic solution. Dissection of the structure-affinity relationships of the inhibitors identifies the hydroxyl groups at positions 1 (Cl-OH) and 4 (C4-OH) of DHNA-CoA or their equivalents as the dominant and minor sites, respectively, for the enzyme-ligand interaction that polarizes or deprotonates the bound ligands to cause the observed spectral changes. In the meantime, spectroscopic studies with active site mutants indicate that C4-OH of the enzyme-bound DHNA-CoA interacts with conserved polar residues Arg-91, Tyr-97, and Tyr-258 likely through a hydrogen bonding network that also includes Ser-161. In addition, site-directed mutation of the conserved Asp-163 to alanine causes a complete loss of the ligand binding ability of the protein, suggesting that the Asp-163 side chain is most likely hydrogen-bonded to Cl-OH of DHNA-CoA to provide the dominant polarizing effect. Moreover, this mutation also completely eliminates the enzyme activity, strongly supporting the possibility that the Asp-163 side chain provides a strong stabilizing hydrogen bond to the tetrahedral oxyanion, which takes a position similar to that of Cl-OH of the enzyme-bound DHNA-CoA and is the second high-energy intermediate in the intracellular Claisen condensation reaction. Interestingly, both Arg-91 and Tyr-97 are located in a disordered loop forming part of the active site of all available DHNA-CoA synthase structures. Their involvement in the interaction with the small molecule ligands suggests that the disordered loop is folded in interaction with the substrates or reaction intermediates, supporting an induced-fit catalytic mechanism for the enzyme

Active Site Binding and Catalytic Role of Bicarbonate in 1,4-Dihydroxy-2-naphthoyl Coenzyme A Synthases from Vitamin K Biosynthetic Pathways

1,4-Dihydroxy-2-naphthoyl coenzyme A (DHNA-CoA) synthase, or MenB, catalyzes a carbon-carbon bond formation reaction in the biosynthesis of both vitamin K1 and K2. Bicarbonate is crucial to the activity of a large subset of its orthologues but lacks a clearly defined structural and mechanistic role. Here we determine the crystal structure of the holoenzymes from Escherichia coli at 2.30 angstrom and Synechocystis sp. PCC6803 at 2.04 angstrom, in which the bicarbonate cofactor is bound to the enzyme active site at a position equivalent to that of the side chain carboxylate of an aspartate residue conserved among bicarbonate-insensitive DHNA-CoA synthases. Binding of the planar anion involves both nonspecific electrostatic attraction and specific hydrogen bonding and hydrophobic interactions. In the absence of bicarbonate, the anion binding site is occupied by a chloride ion or nitrate, an inhibitor directly competing with bicarbonate. These results provide a solid structural basis for the bicarbonate dependence of the enzymatic activity of type DHNA-CoA synthases. The unique location of the bicarbonate ion in relation to the expected position of the substrate a-proton in the enzyme's active site suggests a critical catalytic role for the anionic cofactor as a catalytic base in enolate formation

Evaluating the influence of road lighting on traffic safety at accesses using an artificial neural network

<p><b>Objectives:</b> This article focuses on the effect of road lighting on road safety at accesses to quantitatively analyze the relationship between road lighting and road safety.</p> <p><b>Methods:</b> An artificial neural network (ANN) was applied in this study. This method is one of the most popular machine learning methods and does not require any predefined assumptions. This method was applied using field data collected from 10 road segments in Nanjing, Jiangsu Province, China.</p> <p><b>Results:</b> The results show that the impact of road lighting on road safety at accesses is significant. In addition, road lighting has a greater influence when vehicle speeds are higher or the number of lanes is greater. A threshold illuminance was also found, and the results show that the safety level at accesses will become stable when reaching this value.</p> <p><b>Conclusions:</b> Improved illuminance can decrease the speed variation among vehicles and improve safety levels. In addition, high-grade roads need better illuminance at accesses. A threshold value can also be obtained based on related variables and used to develop scientific guidelines for traffic management organizations.</p