Structure and function of type I copper in multicopper oxidases

金沢大学大学院自然科学研究科物質創成The type I copper center in multicopper oxidases is constructed from 1Cys2His and weakly coordinating 1Met or the non-coordinating 1Phe/1Leu, and it exhibits spectral properties and an alkaline transition similar to those of the blue copper center in blue copper proteins. Since the type I copper center in multicopper oxidases is deeply buried inside the protein molecule, electron transfers to and from type I copper are performed through specific pathways: the hydrogen bond between an amino acid located at the substrate binding site and a His residue coordinating type I copper, and the His-Cys-His sequence connecting the type I copper center and the trinuclear copper center comprised of a type II copper and a pair of type III coppers. The intramolecular electron transfer rates can be tuned by mutating the fourth ligand of type I copper. Further, mutation at the Cys ligand gives a vacant type I copper center and traps the reaction intermediate during the four-electron reduction of dioxygen. © 2007 Birkhäuser Verlag

Community Detection and Growth Potential Prediction Using the Stochastic Block Model and the Long Short-term Memory from Patent Citation Networks

Scoring patent documents is very useful for technology management. However, conventional methods are based on static models and, thus, do not reflect the growth potential of the technology cluster of the patent. Because even if the cluster of a patent has no hope of growing, we recognize the patent is important if PageRank or other ranking score is high. Therefore, there arises a necessity of developing citation network clustering and prediction of future citations. In our research, clustering of patent citation networks by Stochastic Block Model was done with the aim of enabling corporate managers and investors to evaluate the scale and life cycle of technology. As a result, we confirmed nested SBM is appropriate for graph clustering of patent citation networks. Also, a high MAPE value was obtained and the direction accuracy achieved a value greater than 50% when predicting growth potential for each cluster by using LSTM.Comment: arXiv admin note: substantial text overlap with arXiv:1904.1204

Basic and applied features of multicopper oxidases, cueo, bilirubin oxidase, and laccase

金沢大学大学院自然科学研究科物質創成Multicopper oxidases (MCOs) such as CueO, bilirubin oxidase, and laccase contain four Cu centers, type 1 Cu, type II Cu, and a pair of type III Cu\u27s in a protein molecule consisting of three domains with homologous structure to cupredoxin containing only type I Cu. Type I Cu mediates electron transfer between the substrate and the trinuclear Cu center formed by a type II Cu and a pair of type III Cu\u27s, where the final electron acceptor O2 is converted to H2O without releasing activated oxygen species. During the process, O2 is reduced by MCOs such as lacquer lacease and bilirubin oxidase; the reaction intermediate II with a possible doubly OH--bridged structure in the trinuclear Cu center has been detected. The preceding reaction intermediate I has been detected by the reaction of the lacquer lacease in a mixed valence state, at which type I Cu was cuprous and the trinuclear Cu center was fully reduced, and by the reaction of the Cys → Ser mutant for the type I Cu site in bilirubin oxidase and CueO. An acidic amino acid residue located adjacent to the trinuclear Cu center was proved to function as a proton donor to these reaction intermediates. The substrate specificity of MCO for organic substrates is produced by the integrated effects of the shape of the substrate-binding site and the specific interaction of the substrate with the amino acid located adjacent to the His residue coordinating to the type I Cu. In contrast, the substrate specificity of the cuprous oxidase, CueO, is produced by the segment covering the Cu(I)-binding site so as to obstruct the access of organic substrates. Truncating the segment spanning helix 5 to helix 7 greatly reduced the specificity of CueO for Cu(I) and prominently enhanced the low oxidizing activity for the organic substrates, indicating the success of protein engineering to modify the substrate specificity of MCO. © 2007 The Japan Chemical Journal Forum and Wiley Periodicals, Inc

Community Detection and Growth Potential Prediction from Patent Citation Networks

The scoring of patents is useful for technology management analysis. Therefore, a necessity of developing citation network clustering and prediction of future citations for practical patent scoring arises. In this paper, we propose a community detection method using the Node2vec. And in order to analyze growth potential we compare three ''time series analysis methods'', the Long Short-Term Memory (LSTM), ARIMA model, and Hawkes Process. The results of our experiments, we could find common technical points from those clusters by Node2vec. Furthermore, we found that the prediction accuracy of the ARIMA model was higher than that of other models.Comment: arXiv admin note: text overlap with arXiv:1607.00653 by other author

Modifications on the hydrogen bond network by mutations of Escherichia coli copper efflux oxidase affect the process of proton transfer to dioxygen leading to alterations of enzymatic activities

CueO has a branched hydrogen bond network leading from the exterior of the protein molecule to the trinuclear copper center. This network transports protons in the four-electron reduction of dioxygen. We replaced the acidic Glu506 and Asp507 residues with the charged and uncharged amino acid residues. Peculiar changes in the enzyme activity of the mutants relative to the native enzyme indicate that an acidic amino acid residue at position 506 is essential for effective proton transport. The Ala mutation resulted in the formation of a compensatory hydrogen bond network with one or two extra water molecules. On the other hand, the Ile mutation resulted in the complete shutdown of the hydrogen bond network leading to loss of enzymatic activities of CueO. In contrast, the hydrogen bond network without the proton transport function was constructed by the Gln mutation. These results exerted on the hydrogen bond network in CueO are discussed in comparison with proton transfers in cytochrome oxidase. © 2012 Elsevier Inc

Study on dioxygen reduction by mutational modifications of the hydrogen bond network leading from bulk water to the trinuclear copper center in bilirubin oxidase

The hydrogen bond network leading from bulk water to the trinuclear copper center in bilirubin oxidase is constructed with Glu463 and water molecules to transport protons for the four-electron reduction of dioxygen. Substitutions of Glu463 with Gln or Ala were attributed to virtually complete loss or significant reduction in enzymatic activities due to an inhibition of the proton transfer steps to dioxygen. The single turnover reaction of the Glu463Gln mutant afforded the highly magnetically interacted intermediate II (native intermediate) with a broad g = 1.96 electron paramagnetic resonance signal detectable at cryogenic temperatures. Reactions of the double mutants, Cys457Ser/Glu463Gln and Cys457Ser/Glu463Ala afforded the intermediate I (peroxide intermediate) because the type I copper center to donate the fourth electron to dioxygen was vacant in addition to the interference of proton transport due to the mutation at Glu463. The intermediate I gave no electron paramagnetic resonance signal, but the type II copper signal became detectable with the decay of the intermediate I. Structural and functional similarities between multicopper oxidases are discussed based on the present mutation at Glu463 in bilirubin oxidase. © 2014 Elsevier Inc. All rights reserved

Temporal and spatial variations of pulsating auroras in fine-scale obtained from ground-based observations

第2回極域科学シンポジウム/第35回極域宙空圏シンポジウム 11月16日（水） 統計数理研究所 3階リフレッシュフロ

A novel resting form of the trinuclear copper center in the double mutant of a multicopper oxidase, CueO, Cys500Ser/Glu506Ala

A multicopper oxidase, CueO was doubly mutated at its type I copper ligand, Cys500 and an acidic amino acid residue located in the proton transfer pathway, Glu506, to Ser and Ala, respectively. Cys500Ser/Glu506Ala was mainly in a novel resting form to afford the absorption band at ca. 400. nm and an EPR signal with a highly anisotropic character derived from type III copper. However, Cys500Ser/Glu506Ala gave the same reaction intermediate (peroxide intermediate) as that from Cys500Ser and Cys500Ser/Glu506Gln. © 2015 Elsevier Inc.Embargo Period 24 month

Involvement of oxidative stress and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in inflammatory bowel disease

The pathophysiology of inflammatory bowel disease involves excessive immune effects of inflammatory cells against gut microbes. In genetically predisposed individuals, these effects are considered to contribute to the initiation and perpetuation of mucosal injury. Oxidative stress is a fundamental tissue-destructive mechanisms that can occur due to the reactive oxygen species and reactive nitrogen metabolites which are released in abundance from numerous inflammatory cells that have extravasated from lymphatics and blood vessels to the lamina propria. This extravasation is mediated by interactions between adhesion molecules including mucosal addressin cell adhesion molecule-1 and vascular cell adhesion molecule-1 on the surface of lymphocytes or neutrophils and their ligands on endothelial cells. Thus, reactive oxygen species and adhesion molecules play an important role in the development of inflammatory bowel disease. The present review focuses on the involvement of oxidative stress and adhesion molecules, in particular mucosal addressin cell adhesion molecule-1, in inflammatory bowel disease