The Selenium Moiety of Glutathione Peroxidase

Wendel, Albrecht; B, Kerner; Graupe, Klaus

doi:10.1007/978-3-642-67132-6_13

Cited by 15 publications

(10 citation statements)

References 9 publications

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“…On the basis of similar experiments carried out in solution the binding stoichiometry of active-site-directed 14C-labeled haloacetates to native GSH peroxidase has been reported [5,41]. A binding of 2 mol chloroacetate or iodoacetate per tetramer has been obtained, concomitant with complete inactivation of the enzyme.…”

Section: Substrate Binding and Catalytic Mechanismmentioning

confidence: 76%

“…At physiological pH values a selenolate anion rathcr than an undissociated free selenol seems to occur in the reduced enzyme [5,6]. Further evidence is provided by a difference Fourier analysis between inhibited (PROP, JACE, see Table 2) and reduced enzyme, since only a selenolate anion would show considerable nucleophilic reactivity to react with the inhibitors propylenimine or iodoacetic acid.…”

Section: So Hen T Structurementioning

confidence: 99%

“…Glutathione serves as specific electron donor substrate and traces of alimentary selenium provide the prosthetic group, a selenocysteine residue [4,5]. As regards substrate specificity, GSH peroxidase sharply contrasts with the heme peroxidases.…”

mentioning

confidence: 99%

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The Refined Structure of the Selenoenzyme Glutathione Peroxidase at 0.2‐nm Resolution

Epp

Ladenstein

Wendel

1983

European Journal of Biochemistry

657

455

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The crystal structure of bovine erythrocyte glutathione peroxidase has been refined by a combined procedure of restrained crystallographic refinement and energy minimization at 0.20 nm resolution. The final R value at this resolution is 0.178. The r.m.s. deviation of main-chain atoms of the two independently refined monomers is 0.019 nm. The structure at 0.28 nm resolution, which has been determined by multiple isomorphous replacement, served as a starting model.The refined model allowed a detailed survey of the hydrogen-bonding pattern and of the subunit contact areas in the molecule. The model contains 165 solvent molecules per dimer, all taken as water molecules. The mobility of the structure was derived from the individual atomic temperature factors. The complete tetramer, including the active sites, seems to be rather rigid, except for narrow loops near to the N-terminal ends and some p turns exposed to solvent.The active centres of glutathione peroxidase are found in flat depressions on the molecular surface. The catalytically active selenocysteine residues could be located at the N-terminal ends of a helices forming /YG$ substructures together with two adjacent parallel p strands. In the vicinity of the reactive group some aromatic amino acid side-chains could be localized. Especially Trp-148, which could be hydrogen bonded to SeCys-35, may play a functional role during catalysis.The results ofsubstrate and inhibitor binding studies in solution and in the crystalline state could be interpreted by an apparent half-site reactivity of glutathione peroxidase. The enzyme seems to react in the sense of negative cooperativity with dimers being the functional units.Based on difference Fourier analyses of appropriate derivatives a reasonable model of glutathione binding is presented. Among the residues which could be of functional importance are Arg-40, Gln-130 and Arg-167, presumably forming salt bridges and a hydrogen bond to the glutathione molecule.In conclusion, a general picture of a minimal reaction mechanism, which is in good agreement with functional and structural data, is proposed. The main reaction of the catalytic cycle presumably shuttles between the selenolate and the selenenic acid state of SeCys-35.

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Section: Substrate Binding and Catalytic Mechanismmentioning

confidence: 76%

Section: So Hen T Structurementioning

confidence: 99%

See 1 more Smart Citation

The Refined Structure of the Selenoenzyme Glutathione Peroxidase at 0.2‐nm Resolution

Epp

Ladenstein

Wendel

1983

European Journal of Biochemistry

657

455

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“…The link between nutritional science and enzymology was, however, established appreciably later when Flohé et al (1973), intrigued by a preliminary report from Hoekstra's group (Rotruck et al, 1972), identified selenium as a stoichiometric, covalently bound component of glutathione peroxidase (GPx), an enzyme previously demonstrated to dominate mammalian hydroperoxide metabolism (Sies et al, 1972). Selenium proved to be present in this enzyme as a selenocysteine residue (Forstrom et al, 1978, Wendel et al, 1978 that is integrated into the amino acid chain (Günzler et al, 1984). The selenocysteine residue in GPx is responsible for the catalytic efficiency, as demonstrated by site-directed mutagenesis (Rocher et al, 1992), and the X-ray analysis performed by Epp et al (1983) enabled a detailed understanding of the catalytic mechanism (Aumann et al, 1997; see also Figure 1A).…”

Section: Introduction: Some Historical Landmarksmentioning

confidence: 99%

Selenium in Biology: Facts and Medical Perspectives

Köhrl¹,

Brigelius‐Flohé²,

Böck³

et al. 2000

Biological Chemistry

245

143

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Several decades after the discovery of selenium as an essential trace element in vertebrates approximately 20 eukaryotic and more than 15 prokaryotic selenoproteins containing the 21 st proteinogenic amino acid, selenocysteine, have been identified, partially characterized or cloned from several species. Many of these proteins are involved in redox reactions with selenocysteine acting as an essential component of the catalytic cycle. Enzyme activities have been assigned to the glutathione peroxidase family, to the thioredoxin reductases, which were recently identified as selenoproteins, to the iodothyronine deiodinases, which metabolize thyroid hormones, and to the selenophosphate synthetase 2, which is involved in selenoprotein biosynthesis. Prokaryotic selenoproteins catalyze redox reactions and formation of selenoethers in (stress-induced) metabolism and energy production of E. coli, of the clostridial cluster XI and of other prokaryotes. Apart from the specific and complex biosynthesis of selenocysteine, selenium also reversibly binds to proteins, is incorporated into selenomethionine in bacteria, yeast and higher plants, or posttranslationally modifies a catalytically essential cysteine residue of CO dehydrogenase. Expression of individual eukaryotic selenoproteins exhibits high tissue specificity, depends on selenium availability, in some cases is regulated by hormones, and if impaired contributes to several pathological conditions. Disturbance of selenoprotein expression or function is associated with deficiency syndromes (Keshan and Kashin-Beck disease), might contribute to tumorigenesis and atherosclerosis, is altered in several bacterial and viral infections, and leads to infertility in male rodents.

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“…GSH-Px is an enzyme that provides antioxidative defense in mammals by converting hydrogen peroxide to water and lipid hydroperoxides to the corresponding alcohols. Selenium is integrated into GSH-Px as a selenocysteine residue, and is responsible for the catalytic efficiency of the enzyme (Forstrom et al, 1978;Wendel et al, 1978;Rocher et al, 1992;Aumann et al, 1997). GPx1 uses GSH (Glutathione) to reduce ROS (Reactive oxygen species), producing GSSG (Glutathione disulfide) in the process, which is converted back to GSH by the enzyme Glutathione reductase (Reeves et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Characterization of GPX1 and DIO1 Genes in Bubalus Bubalis

Dureja

Singh

Rana

et al. 2012

JBLS

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Selenoprotein genes contain selenium in the form of selenocysteine which is involved in protecting the cells from oxidative stress. Soils in India differ greatly in selenium concentrations affecting feed stuffs for selenium availability. Selenoproteins have recently been identified in variety of living organisms including humans which have 25 selenoprotein genes. Among these families of selenoprotein genes, we sequenced Gpx1 gene (Glutathione peroxidases1) and Dio1 gene (Iodothyronine deiodinases) in Bubalus bubalis. Gpx1 is most abundant and ubiquitously expressed selenoprotein which helps to protect against the damaging effects of hydrogen peroxide and oxygen rich free radicals whereas Dio1 is expressed mainly in liver, thyroid gland and adipose tissue, its main function is to convert tetraiodothyronine (T4) to its active form thyroxine (T3) in the presence of deiodinases enzyme. The main aim of the study was to characterize these two genes and to find out the buffalo specific SNPs. This was accomplished by designing primers using cattle database and sequencing a panel of 24 samples consisting of 6 diverse breeds of buffalo. Gpx1 consisted of 2 exons (Accession ID: JQ031269) while Dio1 comprised 4 exons (Accession ID: JQ791197). In Gpx1 gene, 9 SNPs were recorded and 4 were non synonymous, changing amino acid were distributed equally in both exon. In exon 1, A141G (aa Q5R) and G161A (aa A12T); and in exon 2 C785T (aa R132W) and A808T (aa S139R). In Dio1 gene, 3 non synonymous SNPs were identified at A188G (aa H22R), C215G (aa T31R) and G941A (aa V146I). These SNPs are novel and reported for the first time in Indian buffalo and has a potential for their use in diversity analysis and association with various selenium related traits.

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The Selenium Moiety of Glutathione Peroxidase

Cited by 15 publications

References 9 publications

The Refined Structure of the Selenoenzyme Glutathione Peroxidase at 0.2‐nm Resolution

The Refined Structure of the Selenoenzyme Glutathione Peroxidase at 0.2‐nm Resolution

Selenium in Biology: Facts and Medical Perspectives

Characterization of GPX1 and DIO1 Genes in Bubalus Bubalis

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