Porcine glutathione transferase Alpha 2-2 is a human GST A3-3 analogue that catalyses steroid double-bond isomerization

2010 ◽  
Vol 431 (1) ◽  
pp. 159-167 ◽  
Author(s):  
Natalia Fedulova ◽  
Françoise Raffalli-Mathieu ◽  
Bengt Mannervik
Keyword(s):  
Double Bond ◽  
Glutathione Transferase ◽  
Biological Species ◽  
Glutathione Transferases ◽  
Special Role ◽  
Primary Role ◽  
The Novel ◽  
Protective Function ◽  
Isomerase Activity

A primary role of GSTs (glutathione transferases) is detoxication of electrophilic compounds. In addition to this protective function, hGST (human GST) A3-3, a member of the Alpha class of soluble GSTs, has prominent steroid double-bond isomerase activity. The isomerase reaction is an obligatory step in the biosynthesis of steroid hormones, indicating a special role of hGST A3-3 in steroidogenic tissues. An analogous GST with high steroid isomerase activity has so far not been found in any other biological species. In the present study, we characterized a Sus scrofa (pig) enzyme, pGST A2-2, displaying high steroid isomerase activity. High levels of pGST A2-2 expression were found in ovary, testis and liver. In its functional properties, other than steroid isomerization, pGST A2-2 was most similar to hGST A3-3. The properties of the novel porcine enzyme lend support to the notion that particular GSTs play an important role in steroidogenesis.

scholarly journals Raja yoga within the system of religious-ethical philosophy Of M. V. Lodyzhensky

2020 ◽  
pp. 64-90
Author(s):  
Oleg Viktorovich Solopov
Keyword(s):  
Critical Review ◽  
Scientific Literature ◽  
Critical Assessment ◽  
Special Role ◽  
The Novel ◽  
Ethical Philosophy ◽  
Knowledge Ontology ◽  
Comprehensive Study

This article is dedicated to examination of the characteristics of the doctrine of Raja yoga in interpretation Of M. V. Lodyzhensky. The goal consists in the analysis and reconstruction of the system of Raja yoga within the religious-ethical philosophy of the thinker. In the course of this research, the author resolves a number of problems: examines the system of primary elements of religious-ethical philosophy of M. V. Lodyzhensky; analyzes the sources that affected the formation of views of the philosopher upon Raja yoga; reveals main characteristics of the system of Raja yoga within Lodyzhensky’s philosophy; determines the peculiarities of religious-mystical practice of Raja yoga in the philosophy of M. V. Lodyzhensky; defines the role of Raja-yoga within the system of religious-ethical philosophy of the thinker. The novelty lies in determination of the novel in comparison to the existing in scientific literature categories of M. V. Lodyzhensky’s philosophy and their analysis in the context of system of fundamental sections of philosophical knowledge (ontology, theology, anthropology, epistemology, axiology, ethics); as well as in comprehensive study of the system of Raja yoga in interpretation Of M. V. Lodyzhensky and determination of its role within the structure of his philosophy. It is established that the “core” of the system of religious-ethical philosophy of M. V. Lodyzhensky is the ethics develop ethics and axiology of Hesychasm developed by him. It is proven that the system of metaphysical categories and ideas of the thinker is of synthetic nature and leans on various cultural trends and traditions. The article demonstrates that special role within the system of Lodyzhensky’s philosophy is played by the apologetics of Hesychasm that implies critical review of the non-Christian mystical practices, among which is the examination of Raja yoga. The author underlines the uniqueness of interpretation of Raja yoga in the philosophy M. V. Lodyzhensky, as well as provides critical assessment to his interpretation of the system of Raja yoga.

Targeting human glutathione transferase A3-3 attenuates progesterone production in human steroidogenic cells

2008 ◽  
Vol 414 (1) ◽  
pp. 103-109 ◽  
Author(s):  
Françoise Raffalli-Mathieu ◽  
Carolina Orre ◽  
Mats Stridsberg ◽  
Maryam Hansson Edalat ◽  
Bengt Mannervik
Keyword(s):  
Double Bond ◽  
Glutathione Transferase ◽  
Steroid Hormone ◽  
Cellular Systems ◽  
Double Bond Isomerization ◽  
Steroid Hormone Biosynthesis ◽  
Isomerase Activity ◽  
Cell Extracts ◽  
Hormone Biosynthesis ◽  
Steroidogenic Cells

hGSTA3-3 (human Alpha-class glutathione transferase 3-3) efficiently catalyses steroid Δ5–Δ4 double-bond isomerization in vitro, using glutathione as a cofactor. This chemical transformation is an obligatory reaction in the biosynthesis of steroid hormones and follows the oxidation of 3β-hydroxysteroids catalysed by 3β-HSD (3β-hydroxysteroid dehydrogenase). The isomerization has commonly been ascribed to a supplementary function of 3β-HSD. The present study is the first to provide evidence that hGSTA3-3 contributes to this step in steroid hormone biosynthesis in complex cellular systems. First, we find glutathione-dependent Δ5–Δ4 isomerase activity in whole-cell extracts prepared from human steroidogenic cells. Secondly, effective inhibitors of hGSTA3-3 dramatically decrease the conversion of Δ5-androstene-3,17-dione into Δ4-androstene-3,17-dione in cell lysates. Thirdly, we show that RNAi (RNA interference) targeting hGSTA3-3 expression decreases by 30% the forskolin-stimulated production of the steroid hormone progesterone in a human placental cell line. This effect is achieved at low concentrations of two small interfering RNAs directed against distinct regions of hGSTA3-3 mRNA, and is weaker in unstimulated cells, in which hGSTA3-3 expression is low. The results concordantly show that hGSTA3-3 makes a significant contribution to the double-bond isomerization necessary for steroid hormone biosynthesis and thereby complements the indispensable 3β-hydroxysteroid oxidoreductase activity of 3β-HSD. The results indicate that the lower isomerase activity of 3β-HSD is insufficient for maximal rate of cellular sex hormone production and identify hGSTA3-3 as a possible target for pharmaceutical intervention in steroid hormone-dependent diseases.

scholarly journals Application of Modified ALO to Economic Load Dispatch for Coal Fired Stations

2019 ◽  
Vol 8 (2) ◽  
pp. 2147-2151
Keyword(s):  
Test System ◽  
Optimization Techniques ◽  
Economic Load Dispatch ◽  
Primary Role ◽  
The Novel ◽  
Fuel Cost ◽  
Nature Inspired Algorithm ◽  
Generation Cost ◽  
Ant Lion

This manuscript explores the novel Modified Ant Lion (MALO) Optimization to resolve the load dispatch problem optimally. The primary role of Optimal Economic Load Dispatch (OELD) is to obtain an efficient and economical operation of a power system network. The main aim of performing the OELD is for minimizing the fuel cost of the real power generation when the losses are neglected. An Modified Ant Lion (MALO) Optimization is a narrative nature-inspired algorithm and apes the tracking mechanism of ant lions in life. The random walk of ants, building traps, entrapment of ants in traps, catching preys, and re-building traps are the five main steps involved in the hunting process. The principal objective of OELD is to curtail the total generation cost while honoring effective constraints of accessible generating resources. The anticipated Modified ALO technique is utilized on three and six unit test system to various load demands for solving the load dispatch problem economically. A statistical result clarifies that the anticipated MALO method has lowest fuel cost and superior in quality of solution than other optimization techniques accounted in most latest literature.

The role of Soviet symbols in the national-state identity formation of the Russians

2021 ◽  
Vol 27 (3) ◽  
pp. 82-86
Author(s):  
V. Titov ◽  
Keyword(s):  
Russian Federation ◽  
Soviet Period ◽  
Special Role ◽  
Primary Role ◽  
Right Wing ◽  
State Identity ◽  
National State ◽  
High Importance ◽  
The Russian Federation

This study is devoted to the study of the reasons for the high importance of Soviet symbols in the process of reproduction of the national-state identity of Russians. The research methodology is built by combining structural analysis with secondary processing of quantitative sociological research data. The theoretical foundation of the presented work is formed by the concept of social identity by G. Tajfel and D. Turner. The author has come to the conclusion that the special role of the Soviet symbolic heritage in ensuring the reproduction of the national-state identity of the citizens of the Russian Federation is determined by a complex set of factors, within which the nostalgia of the older generations or the sympathy of a part of the population for communist ideas do not play a primary role. The absence of an attractive image of the future and achievements in the present, comparable in scale with the victories of the past, cause a situation in which the justification of the in-group favoritism of Russians acquires a retrospective vector. As a result, the most significant events of the Soviet period, reflected in the memorial “tradition of the winners,” begin to play the role of a paradigmatic element in the structure of substantiating the prestigious nature of the identity of Russians. The high importance of Soviet symbols is determined by the presence in its semantic basis of such a value element as social justice. The latter is extremely in demand among the broad strata of the population of the Russian Federation at the moment. In addition, the additional significance of the symbols of the USSR is brought by its decommunization in the eyes of some of the bearers of right-wing views. Due to the latter, Soviet symbolism is beginning to be perceived as “imperial”, which gives it a positive character in the eyes of a part of the right-wing public

The Special Role of the Hashemite Kingdom of Jordan in the Muslim Holy Shrines in Jerusalem

2020 ◽  
pp. 1-46
Author(s):  
Victor Kattan
Keyword(s):  
International Law ◽  
Peace Treaty ◽  
Special Role ◽  
Primary Role ◽  
Customary International Law ◽  
Article 9 ◽  
East Jerusalem

Abstract This article explores the meaning of the Jerusalem clause in Article 9(2) of the Israel–Jordan Peace Treaty. It begins by considering the drafting of the clause, before analysing subsequent agreements between Israel, Palestine, and Jordan. The article then turns to history to explore the origins of Jordan’s special role, which amounted to a particular rule of customary international law, from 1967, when Israel recognised that special role after it occupied East Jerusalem, until 1994, when it was codified in the Peace Treaty. The article concludes by explaining that Jordan’s special role is comprised of its custodianship of the Muslim holy shrines in Jerusalem, with its attendant duties of maintaining, protecting, and regulating access to the shrines and that Israel is obligated to give due regard to Jordan’s primary role in the exercise of these duties within the spaces of these shrines.

scholarly journals MMBL proteins: from lectin to bacteriocin

2012 ◽  
Vol 40 (6) ◽  
pp. 1553-1559 ◽  
Author(s):  
Maarten G.K. Ghequire ◽  
Remy Loris ◽  
René De Mot
Keyword(s):  
Binding Activity ◽  
Carbohydrate Binding ◽  
The Novel ◽  
Action Identification ◽  
Protective Function ◽  
Killer Activity ◽  
Gram Positive Bacteria ◽  
Galanthus Nivalis ◽  
Lectin Family

Arguably, bacteriocins deployed in warfare among related bacteria are among the most diverse proteinacous compounds with respect to structure and mode of action. Identification of the first prokaryotic member of the so-called MMBLs (monocot mannose-binding lectins) or GNA (Galanthus nivalis agglutinin) lectin family and discovery of its genus-specific killer activity in the Gram-negative bacteria Pseudomonas and Xanthomonas has added yet another kind of toxin to this group of allelopathic molecules. This novel feature is reminiscent of the protective function, on the basis of antifungal, insecticidal, nematicidal or antiviral activity, assigned to or proposed for several of the eukaryotic MMBL proteins that are ubiquitously distributed among monocot plants, but also occur in some other plants, fish, sponges, amoebae and fungi. Direct bactericidal activity can also be effected by a C-type lectin, but this is a mammalian protein that limits mucosal colonization by Gram-positive bacteria. The presence of two divergent MMBL domains in the novel bacteriocins raises questions about task distribution between modules and the possible role of carbohydrate binding in the specificity of target strain recognition and killing. Notably, bacteriocin activity was also demonstrated for a hybrid MMBL protein with an accessory protease-like domain. This association with one or more additional modules, often with predicted peptide-hydrolysing or -binding activity, suggests that additional bacteriotoxic proteins may be found among the diverse chimaeric MMBL proteins encoded in prokaryotic genomes. A phylogenetic survey of the bacterial MMBL modules reveals a mosaic pattern of strongly diverged sequences, mainly occurring in soil-dwelling and rhizosphere bacteria, which may reflect a trans-kingdom acquisition of the ancestral genes.

scholarly journals The soluble glutathione transferase superfamily: Role of Mu class in Triclabendazole sulphoxide challenge in Fasciola hepatica

2020 ◽  
Author(s):  
Rebekah B. Stuart ◽  
Suzanne Zwaanswijk ◽  
Neil D. MacKintosh ◽  
Boontarikaan Witikornkul ◽  
Mark Prescott ◽  
...  
Keyword(s):  
Glutathione Transferase ◽  
Fasciola Hepatica ◽  
Affinity Purification ◽  
Economic Loss ◽  
Glutathione Transferases ◽  
Parasitic Helminths ◽  
Food Borne ◽  
Production Industry

AbstractFasciola hepatica (liver fluke), a significant threat to food security, causes global economic loss for the livestock production industry and is re-emerging as a food borne disease of humans. In the absence of vaccines the commonly used method of treatment control is by anthelmintics; with only Triclabendazole (TCBZ) currently effective against all stages of F. hepatica in livestock and humans. There is widespread resistance to TCBZ and detoxification by flukes might contribute to the mechanism. However, there is limited Phase I capacity in adult parasitic helminths and the major Phase II detoxification system in adults is the soluble Glutathione transferases (GST) superfamily. Previous global proteomic studies have shown that the levels of Mu class GST from pooled F. hepatica parasites respond under TCBZ-Sulphoxide (TCBZ-SO), the likely active metabolite, challenge during in vitro culture ex-host. We have extended this finding by using a sub-proteomic lead approach to measure the change in the total soluble GST profile (GST-ome) of individual TCBZ susceptible F. hepatica on TCBZ-SO-exposure in vitro culture. TCBZ-SO exposure demonstrated a FhGST-Mu29 and FhGST-Mu26 response following affinity purification using both GSH and S-hexyl GSH affinity resins. Furthermore, a low affinity Mu class GST (FhGST-Mu5) has been identified and recombinantly expressed and represents a novel low affinity mu class GST. Low affinity GST isoforms within the GST-ome was not limited to FhGST-Mu5 with second likely low affinity sigma class GST (FhGST-S2) uncovered through genome analysis. This study represents the most complete Fasciola GST-ome generated to date and has supported the sub proteomic analysis on individual adult flukes.

scholarly journals Fluorescent Bis(guanidine) Copper Complexes as Precursors for Hydroxylation Catalysis

Inorganics ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 114 ◽  
Author(s):  
Florian Strassl ◽  
Alexander Hoffmann ◽  
Benjamin Grimm-Lebsanft ◽  
Dieter Rukser ◽  
Florian Biebl ◽  
...  
Keyword(s):  
Density Functional ◽  
Copper Complexes ◽  
Density Functional Theory Calculations ◽  
Special Role ◽  
The Novel ◽  
X Ray Diffraction ◽  
Functional Theory ◽  
X Ray ◽  
Copper Dioxygen

Bis(guanidine) copper complexes are known for their ability to activate dioxygen. Unfortunately, until now, no bis(guanidine) copper-dioxygen adduct has been able to transfer oxygen to substrates. Using an aromatic backbone, fluorescence properties can be added to the copper(I) complex which renders them useful for later reaction monitoring. The novel bis(guanidine) ligand DMEG2tol stabilizes copper(I) and copper(II) complexes (characterized by single crystal X-ray diffraction, IR spectroscopy, and mass spectrometry) and, after oxygen activation, bis(µ-oxido) dicopper(III) complexes which have been characterized by low-temperature UV/Vis and Raman spectroscopy. These bis(guanidine) stabilized bis(µ-oxido) complexes are able to mediate tyrosinase-like hydroxylation activity as first examples of bis(guanidine) stabilized complexes. The experimental study is accompanied by density functional theory calculations which highlight the special role of the different guanidine donors.

The Art as a Representation of the Existential

2021 ◽  
Vol 32 (4) ◽  
pp. 172
Author(s):  
Sergey Stupin
Keyword(s):  
Homo Sapiens ◽  
Video Art ◽  
Biological Species ◽  
Special Role ◽  
Artistic Creativity ◽  
Art Form ◽  
Interdisciplinary Approaches ◽  
Homo Faber ◽  
First Time

The survey research was fulfilled within the interdisciplinary approaches “anthropology of art” and “existential art science”, updating the concept of “anthropic principle in artistic creativity” demanded by modern humanitarian science. The relevance of the topic is due to the special attention of the art of modern times to existential problems: art practice of the late 19th – the first two decades of the 21st century to the present day in its species, style and genre diversity actively present anthropological terms and meanings. The author of the article emphasizes the immanent nature of the existential foundations of artistic creativity, points to the special role of the phenomenon of Homo faber (man creating) in the composition of Homo sapiens as a biological species, but at the same time pays attention to the role of existential philosophy (starting with S. Kierkegaard), which influenced shaping strategies in world art. The author is interested in ways to represent existential meanings with the plastic capabilities of fine art, procedural forms of neo-avangard, screen arts, theater, poetry, and artistic prose. Special attention is paid to the anthropological potential of the art form — minimal elements of the language of art, plastic nuances of the means of artistic explanation. Within the stereoscopic existential-art-historical approach, the reader is invited to evaluate both the works of modern painting, graphics, sculpture, poetry and fiction, cinema and video art of Russia and the world, which have already become classics and practically unknown to the general public. A detailed panorama of images and languages of art is designed to represent the hypostasis of an existential person — transcending, creating, free, suffering, lonely, loving, frightening, experiencing the experience of death. The mentioned phenomena are considered as structural elements of the system of the existence of human being created by the author, analyzed from an aesthetic and artistic perspective. A similar method of analysis in this context is used for the first time in world science.

scholarly journals Clarification of the role of key active site residues of glutathione transferase Zeta/maleylacetoacetate isomerase by a new spectrophotometric technique

2003 ◽  
Vol 374 (3) ◽  
pp. 731-737 ◽  
Author(s):  
Philip G. BOARD ◽  
Matthew C. TAYLOR ◽  
Marjorie COGGAN ◽  
Michael W. PARKER ◽  
Hoffman B. LANTUM ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Active Site ◽  
Glutathione Transferase ◽  
Salt Bridge ◽  
Side Chain ◽  
Active Site Residues ◽  
Conserved Residues ◽  
Isomerase Activity ◽  
Catalytic Role

hGSTZ1-1 (human glutathione transferase Zeta 1-1) catalyses a range of glutathione-dependent reactions and plays an important role in the metabolism of tyrosine via its maleylacetoacetate isomerase activity. The crystal structure and sequence alignment of hGSTZ1 with other GSTs (glutathione transferases) focused attention on three highly conserved residues (Ser-14, Ser-15, Cys-16) as candidates for an important role in catalysis. Progress in the investigation of these residues has been limited by the absence of a convenient assay for kinetic analysis. In this study we have developed a new spectrophotometric assay with a novel substrate [(±)-2-bromo-3-(4-nitrophenyl)propionic acid]. The assay has been used to rapidly assess the potential catalytic role of several residues in the active site. Despite its less favourable orientation in the crystal structure, Ser-14 was the only residue found to be essential for catalysis. It is proposed that a conformational change may favourably reposition the hydroxyl of Ser-14 during the catalytic cycle. The Cys16→Ala (Cys-16 mutated to Ala) mutation caused a dramatic increase in the Km for glutathione, indicating that Cys-16 plays an important role in the binding and orientation of glutathione in the active site. Previous structural studies implicated Arg-175 in the orientation of α-halo acid substrates in the active site of hGSTZ1-1. Mutation of Arg-175 to Lys or Ala resulted in a significant lowering of the kcat in the Ala-175 variant. This result is consistent with the proposal that the charged side chain of Arg-175 forms a salt bridge with the carboxylate of the α-halo acid substrates.

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