Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.3.5.1 (succinate dehydrogenase)
8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have isolated a homolog for the flavoprotein subunit of succinate dehydrogenase [succinate:(acceptor) oxidoreductase, EC 1.3.99.1] from Saccharomyces cerevisiae and used the obtained peptide sequences to clone and characterize the corresponding gene. It contained an open reading frame of 1923 base pairs and encoded a protein of 640 amino acids (M(r), 70,238) that showed approximately 49% and approximately 28% identity with the Escherichia coli and Bacillus subtilis enzymes, respectively. All features of the FAD cofactor binding site were completely conserved. Comparison of the deduced protein sequence with the N-terminal sequence determined from the isolated protein revealed an N-terminal extension of 28 amino acids that presumably represents a mitochondrial signal sequence. After in vitro transcription and translation, the preprotein was efficiently imported into isolated yeast mitochondria, cleaved to its mature form, and assembled into the membrane-bound succinate dehydrogenase complex.
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PMID:Primary structure, import, and assembly of the yeast homolog of succinate dehydrogenase flavoprotein. 151 27

Succinate dehydrogenase (EC 1.3.99.1) of the mitochondrial inner membrane is a four-subunit membrane-bound enzyme that catalyzes the oxidation of succinate to fumarate and the transfer of electrons into the electron transport chain to oxygen. The catalytic domain of the enzyme is composed of a flavoprotein subunit which contains a covalently attached FAD cofactor and an iron-sulfur subunit with three nonidentical iron-sulfur clusters. We have isolated a complete genomic clone for the flavoprotein subunit of the succinate dehydrogenase from Saccharomyces cerevisiae and determined its nucleotide sequence. The sequence predicts a protein of 70,185 Da (640 amino acids) that shows more similarity to the Escherichia coli succinate dehydrogenase flavoprotein subunit than it does to the only other mitochondrial homologue, the human flavoprotein subunit. The yeast flavoprotein subunit precursor was synthesized in a cell-free translation system and shown to possess a mitochondrial targeting sequence that directs its import into isolated, energized mitochondria where it is processed by the matrix-localized protease. The genes for the flavoprotein and the iron-sulfur subunits reside on different chromosomes and hence form different transcriptional units.
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PMID:Isolation and nucleotide sequence of the Saccharomyces cerevisiae gene for the succinate dehydrogenase flavoprotein subunit. 157 80

Menaquinol-fumarate oxidoreductase of Escherichia coli is a four-subunit membrane-bound complex that catalyzes the final step in anaerobic respiration when fumarate is the terminal electron acceptor. The enzyme is structurally and catalytically similar to succinate dehydrogenase (succinate-ubiquinone oxidoreductase) from both procaryotes and eucaryotes. Both enzymes have been proposed to contain an essential cysteine residue at the active site based on studies with thiol-specific reagents. Chemical modification studies have also suggested roles for essential histidine and arginine residues in catalysis by succinate dehydrogenase. In the present study, a combination of site-directed mutagenesis and chemical modification techniques have been used to investigate the role(s) of the conserved histidine 232, cysteine 247, and arginine 248 residues of the flavorprotein subunit (FrdA) in active site function. A role for His-232 and Arg-248 of FrdA is shown by loss of both fumarate reductase and succino-oxidase activities following site-directed substitution of these particular amino acids. Evidence is also presented that suggests a second arginine residue may form part of the active site. Potential catalytic and substrate-binding roles for arginine are discussed. The effects of removing histidine-232 of FrdA are consistent with its proposed role as a general acid-base catalyst. The fact that succinate oxidation but not fumarate reduction was completely lost, however, might suggest that alternate proton donors substitute for His-232. The data confirm that cysteine 247 of FrdA is responsible for the N-ethylmaleimide sensitivity shown by fumarate reductase but is not required for catalytic activity or the tight-binding of oxalacetate, as previously thought.
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PMID:Identification of active site residues of Escherichia coli fumarate reductase by site-directed mutagenesis. 185 94

Cadmium ions inhibit membrane-bound succinate dehydrogenase with a second-order rate constant of 10.42 mM-1 s-1 at pH 7.35 and 25 degrees C. Succinate and malonate protect the enzyme against cadmium ion inhibition. The protection pattern exerted by succinate and malonate suggests that the group modified by cadmium is located at the active site. The pH curve of inactivation by Cd2+ indicates the involvement of an amino acid residue with pKa of 7.23.
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PMID:Study of the interaction of cadmium with membrane-bound succinate dehydrogenase. 205 Jun 57

An increase of proton permeability, creation of the possibility for the superoxide radical O2-. to escape and a decrease in the oxidation rate of acetyl-CoA due to the stress origin with such membrane-bound enzymes as succinate dehydrogenase and cytochrome oxidase remaining as active as they were, have been observed under the myocardial necroses reproduced after the endured stress in the internal mitochondrial membrane of the "non-ischemized" division of the left ventricle of the heart. Against a background of mitochondria denergization the content of non-esterified fatty acids in blood increases mainly as a result of the influx of non-esterified fatty acids of membrane origin.
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PMID:[Activity of enzymes of the internal membrane of heart mitochondria and spectrum of blood fatty acids during myocardial necrosis reproduced after the stress]. 215 66

Merocyanine 540 (MC 540) is a photosensitizing dye that is used clinically for the purging of autologous bone marrow grafts and preclinically for the inactivation of enveloped viruses in blood products. Its mechanism of action is not yet well understood. This paper investigates the sites of MC 540-mediated photodamages in L1210 leukemia cells by examining the effects of MC 540-sensitized photoirradiation on several soluble and membrane-bound marker enzymes. When exposed to MC 540 and white light under a standard set of conditions, the activities of Na+/K(+)-ATPase, Mg2(+)-ATPase, and 5'-nucleotidase (three plasma membrane-bound enzymes) were reduced by 54, 49, and 55%, respectively. None of the intracellular enzymes included in this survey was affected by MC 540-sensitized photoirradiation as long as the plasma membrane remained intact. The two soluble enzymes, lactate dehydrogenase and malate dehydrogenase, remained refractory to MC 540-sensitized photoirradiation even after the plasma membrane had been disrupted. By contrast, the activities of the membrane-bound enzymes, NADPH-cytochrome c reductase and succinate dehydrogenase, were reduced in cell lysates by 55 and 81%, respectively. Purified NADPH-cytochrome c reductase was about 3 times less sensitive than the microsomal enzyme, suggesting that the membrane environment facilitated photoinactivation. The MC 540-sensitized photoinactivation of enzymes was accelerated in the presence of deuterium oxide and inhibited if oxygen in the medium was displaced by nitrogen or azide was added to the medium. Taken together, these data support the view that the plasma membrane is a major target of MC 540-mediated photodamages, that the inactivation of membrane-bound enzymes is an oxidative process, and that at least some photodynamic damages are mediated by type II chemistry.
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PMID:Merocyanine 540-sensitized photoinactivation of soluble and membrane-bound enzymes in L1210 leukemia cells. 217 31

The triarylmethane derivative Victoria Blue-BO (VB-BO) and the chalcogenapyrylium (CP) dyes have potential for use in photochemotherapy, because they are taken up by the mitochondria of malignant cells and cause cell death. To clarify the mechanism of cell killing we examined the phototoxic effects of VB-BO and a series of three CP dyes on bioenergetic function in isolated rat liver mitochondria. Without photoirradiation, and irrespective of the respiratory substrate used, each of the compounds tested induced some uncoupling of oxidative phosphorylation. Visible irradiation of VB-BO produced an inhibition of mitochondrial respiration when glutamate plus malate, but not succinate, was used as the respiratory substrate. With photoirradiation VB-BO was also shown to inhibit rotenone-sensitive NADH-cytochrome c reductase activity, but it had no effect on succinate-cytochrome c reductase activity. These data indicate that photoactivation of VB-BO produces selective inhibition of mitochondrial respiratory complex I. Photoirradiation of the CP dyes inhibited both complex I and complex II initiated respiratory activity. With photoirradiation, the CP dyes also inhibited both NADH- and succinate-cytochrome c reductase activities, as well as other membrane-bound enzymes, cytochrome c oxidase and succinate dehydrogenase, but not the mitochondrial matrix enzyme, citrate synthetase, or the cytosolic enzyme, lactate dehydrogenase. alpha-Tocopherol protected bioenergetic activities against CP dye photodamage. These results suggest that mitochondrial photosensitization by CP compounds is mediated by the production of membrane-damaging singlet oxygen which causes nonspecific damage to membranes and membrane-bound enzymes.
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PMID:Mitochondrial toxicity of cationic photosensitizers for photochemotherapy. 217 36

Succinate, malate, and lactate dehydrogenase were demonstrated histochemically and measured histophotometrically in the heart and skeletal muscle (m. extensor digitorum longus and m. soleus) of rats at different ages. To prove the value of histophotometry, the enzymes of the tissues were estimated biochemically. The gel film technique cannot sufficiently prevent the diffusion of the soluble enzymes (malate-, lactate dehydrogenase) out of the tissue sections. Because of the different mobility, various isoenzymes, histophotometry cannot give reliable results. But, as far as membrane-bound dehydrogenases (succinate dehydrogenase) are concerned, histophotometry is the method of choice for basic measurements as in routine practical work, especially with tissues where the enzyme activities are heterogeneously distributed, e.g. in different types of muscle fibres in skeletal muscles.
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PMID:Histophotometry--the method of choice in quantifying dehydrogenase histochemistry. 251 99

The membrane-bound succinate dehydrogenase (SDH; EC 1.3.99.1) of Bacillus pumilus strain 5 was investigated as succinate:ferricyanide oxidoreductase activity at 27 degrees C. A Km of 8.3 x 10(-3) M was obtained, and the Vmax was 1.8 x 10(-6) mole succinate dehydrogenated min-1 mg-1 membrane protein, at a substrate (succinate) concentration below 40 x 10(-3) M. Above this succinate concentration the Km was 102 x 10(-3) M and the Vmax was 3.7 x 10(-6) mole succinate min-1 mg-1 membrane protein. Para-benzoquinone or 2,4-dinitrophenylhydrazine, in micromolar amounts inhibited the enzyme by serving as an electron sink. Hydroxyl radical (OH.) scavengers, mannitol and benzoate, activated the enzyme, while superoxide dismutase (SOD) had no effect on the enzyme. Thus, the mechanism of electron transfer from succinate to Fe(CN)3-(6) through SDH does not involve superoxide (O2-) as a rate-limiting intermediate.
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PMID:Membrane-bound succinate dehydrogenase of Bacillus pumilus strain 5: effects of modulators of monoelectron transfer. 251 38

Succinate dehydrogenase is a membrane-bound metallo-flavo-enzyme containing a bi- (S-1), a tri- (S-3) and a tetranuclear (S-2) iron-sulfur cluster. The catalytic portion of the enzyme contains two distinct subunits designated Fp and Ip. Using concentrated extracts from mutant strains of Bacillus subtilis it was demonstrated, by using low temperature EPR, that cluster S-2 can be assembled in a soluble succinate dehydrogenase. In a mutant with a truncated Ip subunit which lacks 7 of the 11 conserved cysteine residues, cluster S-1 lacked the spin relaxation properties attributable to an adjacent cluster S-2. These data are consistent with a model where one or more cysteine residues from the middle set of 4 conserved cysteines in the Ip subunit are ligands to the tetranuclear cluster.
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PMID:EPR characterization of soluble fragments of succinate dehydrogenase from mutant strains of Bacillus subtilis. 255 79


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