Single- and Two-Electron Reduction of Nitroaromatic Compounds by Flavoenzymes: Mechanisms and Implications for Cytotoxicity

Nitroaromatic compounds (ArNO2) maintain their importance in relation to industrial processes, environmental pollution, and pharmaceutical application. The manifestation of toxicity/therapeutic action of nitroaromatics may involve their single- or two-electron reduction performed by various flavoenzymes and/or their physiological redox partners, metalloproteins. The pivotal and still incompletely resolved questions in this area are the identification and characterization of the specific enzymes that are involved in the bioreduction of ArNO2 and the establishment of their contribution to cytotoxic/therapeutic action of nitroaromatics. This review addresses the following topics: (i) the intrinsic redox properties of ArNO2, in particular, the energetics of their single- and two-electron reduction in aqueous medium; (ii) the mechanisms and structure-activity relationships of reduction in ArNO2 by flavoenzymes of different groups, dehydrogenases-electrontransferases (NADPH:cytochrome P-450 reductase, ferredoxin:NADP(H) oxidoreductase and their analogs), mammalian NAD(P)H:quinone oxidoreductase, bacterial nitroreductases, and disulfide reductases of different origin (glutathione, trypanothione, and thioredoxin reductases, lipoamide dehydrogenase), and (iii) the relationships between the enzymatic reactivity of compounds and their activity in mammalian cells, bacteria, and parasites.

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Identification and characterization of Fep15, a new selenocysteine-containing member of the Sep15 protein family

Biochemical Journal ◽

10.1042/bj20051569 ◽

2006 ◽

Vol 394 (3) ◽

pp. 575-579 ◽

Cited By ~ 28

Author(s):

Sergey V. Novoselov ◽

Deame Hua ◽

Alexey V. Lobanov ◽

Vadim N. Gladyshev

Keyword(s):

Mammalian Cells ◽

Insertion Sequence ◽

Phylogenetic Analyses ◽

Dependent Manner ◽

Putative Active Site ◽

A Genome ◽

Sequence Elements ◽

Identification And Characterization ◽

Insertion Sequence Elements

Sec (selenocysteine) is a rare amino acid in proteins. It is co-translationally inserted into proteins at UGA codons with the help of SECIS (Sec insertion sequence) elements. A full set of selenoproteins within a genome, known as the selenoproteome, is highly variable in different organisms. However, most of the known eukaryotic selenoproteins are represented in the mammalian selenoproteome. In addition, many of these selenoproteins have cysteine orthologues. Here, we describe a new selenoprotein, designated Fep15, which is distantly related to members of the 15 kDa selenoprotein (Sep15) family. Fep15 is absent in mammals, can be detected only in fish and is present in these organisms only in the selenoprotein form. In contrast with other members of the Sep15 family, which contain a putative active site composed of Sec and cysteine, Fep15 has only Sec. When transiently expressed in mammalian cells, Fep15 incorporated Sec in an SECIS- and SBP2 (SECIS-binding protein 2)-dependent manner and was targeted to the endoplasmic reticulum by its N-terminal signal peptide. Phylogenetic analyses of Sep15 family members suggest that Fep15 evolved by gene duplication.

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Identification and Characterization of Carbohydrate Molecules in Mammalian Cells Recognized by Dengue Virus Type 2

The Journal of Biochemistry ◽

10.1093/jb/mvj067 ◽

2006 ◽

Vol 139 (3) ◽

pp. 607-614 ◽

Cited By ~ 50

Author(s):

Chie Aoki ◽

Kazuya I.P.J. Hidari ◽

Saki Itonori ◽

Akihiro Yamada ◽

Naonori Takahashi ◽

...

Keyword(s):

Dengue Virus ◽

Virus Type ◽

Mammalian Cells ◽

Identification And Characterization ◽

Dengue Virus Type 2

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Identification and characterization of mitochondrial abasic (AP)-endonuclease in mammalian cells

Nucleic Acids Research ◽

10.1093/nar/gkl177 ◽

2006 ◽

Vol 34 (7) ◽

pp. 2067-2076 ◽

Cited By ~ 106

Author(s):

R. Chattopadhyay

Keyword(s):

Mammalian Cells ◽

Ap Endonuclease ◽

Identification And Characterization

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[16]Identification and characterization of transcription factors from mammalian cells

Human Molecular Genetics - Methods in Molecular Genetics ◽

10.1016/s1067-2389(96)80049-5 ◽

1996 ◽

pp. 298-320 ◽

Cited By ~ 5

Author(s):

Guang L. Wang ◽

Gregg L. Semenza

Keyword(s):

Transcription Factors ◽

Mammalian Cells ◽

Identification And Characterization

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Beyond Lipid Signaling: Pleiotropic Effects of Diacylglycerol Kinases in Cellular Signaling

International Journal of Molecular Sciences ◽

10.3390/ijms21186861 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6861

Author(s):

Jae Ang Sim ◽

Jaehong Kim ◽

Dongki Yang

Keyword(s):

Phosphatidic Acid ◽

Biological Networks ◽

Mammalian Cells ◽

Recent Progress ◽

Cellular Signaling ◽

Diacylglycerol Kinase ◽

Review Article ◽

Pathological Conditions ◽

Identification And Characterization

The diacylglycerol kinase family, which can attenuate diacylglycerol signaling and activate phosphatidic acid signaling, regulates various signaling transductions in the mammalian cells. Studies on the regulation of diacylglycerol and phosphatidic acid levels by various enzymes, the identification and characterization of various diacylglycerol and phosphatidic acid-regulated proteins, and the overlap of different diacylglycerol and phosphatidic acid metabolic and signaling processes have revealed the complex and non-redundant roles of diacylglycerol kinases in regulating multiple biochemical and biological networks. In this review article, we summarized recent progress in the complex and non-redundant roles of diacylglycerol kinases, which is expected to aid in restoring dysregulated biochemical and biological networks in various pathological conditions at the bed side.

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Identification and characterization of alternatively spliced variants of DNA methyltransferase 3a in mammalian cells

Gene ◽

10.1016/s0378-1119(02)00976-9 ◽

2002 ◽

Vol 298 (1) ◽

pp. 91-99 ◽

Cited By ~ 33

Author(s):

Daniel J. Weisenberger ◽

Mihaela Velicescu ◽

Miguel A. Preciado-Lopez ◽

Felicidad A. Gonzales ◽

Yvonne C. Tsai ◽

...

Keyword(s):

Mammalian Cells ◽

Dna Methyltransferase ◽

Alternatively Spliced ◽

Dna Methyltransferase 3A ◽

Identification And Characterization

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Identification and characterization of human immunodeficiency virus type 1 gag-pol fusion protein in transfected mammalian cells.

Journal of Virology ◽

10.1128/jvi.65.5.2751-2756.1991 ◽

1991 ◽

Vol 65 (5) ◽

pp. 2751-2756 ◽

Cited By ~ 9

Author(s):

C Peng ◽

N T Chang ◽

T W Chang

Keyword(s):

Human Immunodeficiency Virus ◽

Fusion Protein ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Mammalian Cells ◽

Immunodeficiency Virus ◽

Identification And Characterization

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Identification and characterization of natural microbial products that alter the free d -aspartate content of mammalian cells

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2015.11.073 ◽

2016 ◽

Vol 26 (2) ◽

pp. 556-560

Author(s):

Masumi Katane ◽

Yuusuke Kaneko ◽

Misaki Watanabe ◽

Yuki Doi ◽

Taku Tanaka ◽

...

Keyword(s):

Mammalian Cells ◽

Microbial Products ◽

Identification And Characterization

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Identification and characterization of Gbeta3s2, a novel splice variant of the G-protein beta3 subunit

Biochemical Journal ◽

10.1042/bj20021208 ◽

2003 ◽

Vol 371 (1) ◽

pp. 223-232 ◽

Cited By ~ 34

Author(s):

Dieter ROSSKOPF ◽

Iris MANTHEY ◽

Christiane HABICH ◽

Marzena KIELBIK ◽

Andreas EISENHARDT ◽

...

Keyword(s):

G Protein ◽

Splice Variant ◽

Mammalian Cells ◽

Molecular Mechanisms ◽

Biologically Active ◽

Complex Phenotype ◽

825T Allele ◽

Propeller Blades ◽

Identification And Characterization

The T-allele of a polymorphism (C825T) in the gene for the G-protein β3 subunit (GNB3) is associated with cardiovascular and metabolic disorders, distinct cellular features and altered drug responses. The molecular mechanisms that give rise to this complex phenotype have been linked to the occurrence of Gβ3s, a splice variant of GNB3. Gβ3s is predominantly expressed in cells with the 825T-allele. In the present study we describe the identification and characterization of an additional Gβ3 splice variant referred to as Gβ3s2. Its mRNA is expressed in heart, blood cells and tumour tissue, and its expression is also tightly associated with the GNB3 825T-allele. Gβ3s2 is generated by alternative splicing using non-canonical splice sites. Gβ subunits belong to the family of propeller proteins and consist of seven regular propeller blades. Transcripts for Gβ3s2 are lacking 129bp of the coding sequence of the wild-type Gβ3 protein. Thus the predicted structure consists of only six propeller blades, which resembles the structure of Gβ3s. Co-immunoprecipitation analyses indicated that Gβ3s2 dimerizes with different Gγ subunits, e.g. Gγ5, Gγ8C and Gγ12. In Sf9 insect cells, expression of Gβ3s2 together with Gγ12 enhances receptor-stimulated activation of Gαi2. Expression of Gβ3s2 in mammalian cells activated the mitogen-activated protein kinase cascade. Together, these results suggest that Gβ3s2 is a biologically active Gβ variant which may play a role in the manifestation of the complex phenotype associated with the 825T-allele.

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