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evolution
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the enzyme as respiratory complex II belongs to the succinate:quinone oxidoreductases superfamily that comprises succinate:quinone reductases and quinol:fumarate reductases
evolution
enzyme QFR is a member of the complex II superfamily and is composed of FrdABCD subunits
evolution
Megalodesulfovibrio gigas
one menaquinone molecule is bound near heme bL in the hydrophobic subunit C. This location of the menaquinone-binding site differs from the menaquinol-binding cavity proposed previously for QFR from Wolinella succinogenes. The observed bound menaquinone might serve as an additional redox cofactor to mediate the proton-coupled electron transport across the membrane
evolution
quinol:fumarate reductase (QFR) is a member of the respiratory complex II superfamily
evolution
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the SDH function is regulated through distinct molecular pathways in different species
evolution
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the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells
evolution
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the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells
evolution
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the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells
evolution
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the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells
evolution
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the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells
evolution
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the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells
evolution
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the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells
evolution
the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells
evolution
the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells
evolution
the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells
evolution
Megalodesulfovibrio gigas DSM 1382
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one menaquinone molecule is bound near heme bL in the hydrophobic subunit C. This location of the menaquinone-binding site differs from the menaquinol-binding cavity proposed previously for QFR from Wolinella succinogenes. The observed bound menaquinone might serve as an additional redox cofactor to mediate the proton-coupled electron transport across the membrane
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evolution
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the enzyme as respiratory complex II belongs to the succinate:quinone oxidoreductases superfamily that comprises succinate:quinone reductases and quinol:fumarate reductases
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malfunction
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the frequency of polymorphisms of SDHs, hypoxia-inducible factor type 1 and angiotensin converting enzyme genes is compared between 40 subjects with intolerance to high altitude and a low hypoxic ventilatory response at exercise and 41 subjects without intolerance to high altitude and a high hypoxic ventilatory. No significant association between low or high hypoxic ventilatory response and the allele frequencies for nine single nucleotide polymorphisms in the SDHD and SDHB genes, the ACE insertion/deletion polymorphism and four single nucleotide polymorphisms in the hypoxia-inducible factor type 1 a gene is found. No clear association is found between gene variants involved in oxygen sensing and chemoresponsiveness, although some mutations in the SDHB and SDHD genes deserve further investigations in a larger population
malfunction
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the presentation of three synchronous extra-adrenal abdominal paragangliomas in an adolescent boy who carries a germline mutation in the SDHB gene are reported. Loss of heterozygosity of this allele is demonstrated by direct sequencing of DNA from two of his tumors, confirming loss of tumor suppressor function in the pathogenesis of these paragangliomas
malfunction
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the succinate:ubiquinone oxidoreductase activity of the mitochondrial respiratory complex II is specifically impaired by reactive oxygen species without affecting the second enzymatic activity of this complex as a succinate dehydrogenase. The different pro-apoptotic agents responsible for complex II inhibition lead to mitochondrial matrix acidification. Complex II contributes to apoptosis induction only when the SQR activity is inhibited while the SDH activity is still fully functioning,creating an uncoupling phenomenon at the complex II level. The association of an active SDH activity with an inhibited SQR function is not possible, rendering complex II incapable of apoptosis induction and promoting tumourigenesis
malfunction
impaired function of SDH results in deleterious disorders from cancer to neurodegeneration. Defective SDH leads to tumorigenesis, where accumulated succinate promotes HIF-1 stabilization. In humans, another regulatory mechanism through alternative splicing of SDHC transcript is reported in which a shorter isoform of SDHC (DELTA5 lacking exon 5) is produced which lacks heme binding region and therefore has no function. This results in significant downregulation of SDH complex. This variant of SDHC may, therefore, act as a dominant-negative inhibitor of full-length SDHC. DELAT5 may have a role in the pathogenesis of tumorigenesis associated with the malfunction of SDH. A posttranscriptional regulation has been described in late stages of lung cancer in which miR-210 (a microRNA) is overexpressed in normoxia. miR-210 targets SDHD and other transcripts of complex I and II such as NDUAF4 eventually leading to mitochondrial dysfunction and cell death. miR-210-dependent targeting of SDHD transcript activates HIF-1 and in agreement with earlier findings links loss-of-function SDH mutations to HIF-1 stabilization. A mutation in K547 of SDHA (which is typically desuccinylated by SIRT5) renders SDHA unable to interact with SDH5 and thereby made SDH inactive. Furthermore, SIRT5 promotes clear cell renal cell carcinoma (ccRCC) proliferation through inactivation of SDH and switching metabolism to aerobic glycolysis
malfunction
the yeast cells lacking SDH5 gene can grow in fermentative mode (i.e. in glucose), but fail to grow in respiratory mode (e.g. in glycerol) which is an indication of a defective oxidative phosphorylation. This phenotype can be rescued by expression of SDH5. Other phenotypes of sdh5DELTA yeast cells include: substantially decreased levels of all four SDH subunits, impaired oxygen consumption (similar to the respiratory-deficient sdh1DELTA cells), respiration-related phenotypes of H2O2 hypersensitivity and reduced chronological life-span. Another phenotype is acetate hyper-excretion which is shared by four other TCA cycle mutants. A yeast strain lacking SDHAF1 homologue Sdh6 is OXPHOS incompetent. Transformation of this strain with YDR379C-A variants corresponding to the human mutant alleles do not recover OXPHOS growth, indicating that these mutations cause the disease. Yeast lacking SDHAF3 exhibits defective SDH activity and reduced levels of Sdh2
metabolism
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enzymatic activity, quinone content and complex II subunit composition in mitochondria of lung stage L3 (LL3) Ascaris suum larvae is examined. Lung stage L3 Ascaris suum larvae mitochondria show higher quinolfumarate reductase activity than mitochondria of Ascaris suum at other stages. Ubiquinone content in lung stage L3 larvae mitochondria is more abundant than rhodoquinone. It is shown that lung stage L3 larvae mitochondria contain larval flavoprotein subunit (Fp) and adult flavoprotein subunit at a ratio of 1:0.56, and that most lung stage L3 larvae cytochrome b containing subunits CybS are of the adult form. This clearly indicates that the rearrangement of complex II begins with a change in the isoform of the anchor CybS subunit, followed by a similar change in the Fp subunit
metabolism
Megalodesulfovibrio gigas
QFR catalyzes the coupled reduction of fumarate to succinate with the oxidation of hydroquinone (quinol) to quinone on opposite sides of the inner cytoplasmic membrane. The reverse reaction, namely, the coupled oxidation of succinate to fumarate with the reduction of quinone to quinol, is catalyzed by the well-studied succinate:quinone reductase (SQR, EC 1.3.5.1), often referred to as complex II in the respiratory electron-transport chain of aerobic organisms
metabolism
succinate dehydrogenase (SDH) is one of the most important enzymes involved in the in three cellular processes: glycolysis, the tricarboxylic acid cycle (TCA cycle, Krebs cycle) and oxidative phosphorylation (OXPHOS). SDH, also known as complex II or succinate:ubiquinone oxidoreductase (SQR) is a unique enzyme in four ways: first, it is involved in both the TCA and OXPHOS in mitochondria. Second, all the genes for mitochondrial SDH are nuclear. Third, it is the only membrane-bound component of TCA cycle. Fourth, it is the smallest and the only complex of mitochondrial electron transport chain (ETC) which does not directly extrude protons. But it contributes to the proton gradient by supplying reducing equivalents resulting from succinate metabolism. The reducing equivalents are then transported through the ubiquinone pool thereby enabling proton extrusion by complex III and IV
metabolism
succinate dehydrogenase (SDH) is one of the most important enzymes involved in the three cellular processes: glycolysis, the tricarboxylic acid cycle (TCA cycle, Krebs cycle) and oxidative phosphorylation (OXPHOS). SDH, also known as complex II or succinate:ubiquinone oxidoreductase (SQR) is a unique enzyme in four ways: first, it is involved in both the TCA and OXPHOS in mitochondria. Second, all the genes for mitochondrial SDH are nuclear. Third, it is the only membrane-bound component of TCA cycle. Fourth, it is the smallest and the only complex of mitochondrial electron transport chain (ETC) which does not directly extrude protons. But it contributes to the proton gradient by supplying reducing equivalents resulting from succinate metabolism. The reducing equivalents are then transported through the ubiquinone pool thereby enabling proton extrusion by complex III and IV. Succinate is oxidized to fumarate in the TCA cycle by SDHA-B and the electrons derived are transported to ubiquinone (coenzyme Q) and then to complex III. The electrons along the way reduce FAD of SDHA subunit and move through Fe-S clusters in SDHB subunit and then reduce ubiquinone before transfer to complex III
metabolism
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succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP
metabolism
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succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP
metabolism
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succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP
metabolism
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succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP
metabolism
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succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP
metabolism
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succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP
metabolism
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succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP
metabolism
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succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP
metabolism
succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP
metabolism
succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP
metabolism
succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP
metabolism
succinate:quinone oxidoreductase (SQR) functions in energy metabolism, coupling the tricarboxylic acid cycle and electron transport chain in bacteria and mitochondria. The biogenesis of flavinylated SdhA, the catalytic subunit of SQR, is assisted by a highly conserved assembly factor termed SdhE in bacteria via an unknown mechanism. Bacterial SdhE proteins, and their mitochondrial homologues, seem to be assembly chaperones that constrain the conformation of SdhA to facilitate efficient flavinylation while regulating succinate dehydrogenase activity for productive biogenesis of SQR
metabolism
Megalodesulfovibrio gigas DSM 1382
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QFR catalyzes the coupled reduction of fumarate to succinate with the oxidation of hydroquinone (quinol) to quinone on opposite sides of the inner cytoplasmic membrane. The reverse reaction, namely, the coupled oxidation of succinate to fumarate with the reduction of quinone to quinol, is catalyzed by the well-studied succinate:quinone reductase (SQR, EC 1.3.5.1), often referred to as complex II in the respiratory electron-transport chain of aerobic organisms
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physiological function
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the iron-sulfur subunit (SdhB) of mitochondrial succinate dehydrogenase is encoded by a split and rearranged nuclear gene in Euglena gracilis and trypanosomatids, an example of a rare genomic character. The two subgenic modules are transcribed independently and the resulting mRNAs appear to be independently translated, with the two protein products imported into mitochondria, based on the presence of predicted mitochondrial targeting peptides. Although the inferred protein sequences are in general very divergent from those of other organisms, all of the required iron-sulfur cluster-coordinating residues are present. Moreover, the discontinuity in the euglenozoan SdhB sequence occurs between the two domains of a typical, covalently continuous SdhB, consistent with the inference that the euglenozoan half proteins are functional
physiological function
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the iron-sulfur subunit (SdhB) of mitochondrial succinate dehydrogenase is encoded by a split and rearranged nuclear gene in Euglena gracilis and trypanosomatids, an example of a rare genomic character. The two subgenic modules are transcribed independently and the resulting mRNAs appear to be independently translated, with the two protein products imported into mitochondria, based on the presence of predicted mitochondrial targeting peptides. Although the inferred protein sequences are in general very divergent from those of other organisms, all of the required iron-sulfur cluster-coordinating residues are present. Moreover, the discontinuity in the euglenozoan SdhB sequence occurs between the two domains of a typical, covalently continuous SdhB, consistent with the inference that the euglenozoan half proteins are functional
physiological function
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the iron-sulfur subunit (SdhB) of mitochondrial succinate dehydrogenase is encoded by a split and rearranged nuclear gene in Euglena gracilis and trypanosomatids, an example of a rare genomic character. The two subgenic modules are transcribed independently and the resulting mRNAs appear to be independently translated, with the two protein products imported into mitochondria, based on the presence of predicted mitochondrial targeting peptides. Although the inferred protein sequences are in general very divergent from those of other organisms, all of the required iron-sulfur cluster-coordinating residues are present. Moreover, the discontinuity in the euglenozoan SdhB sequence occurs between the two domains of a typical, covalently continuous SdhB, consistent with the inference that the euglenozoan half proteins are functional
physiological function
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using pharmacological and siRNA methodologies it is shown that increased methylation of histone H3 is a general consequence of SDH loss-of-function in cultured mammalian cells and can be reversed by overexpression of the JMJD3 histone demethylase. ChIP analysis reveals that the core promoter of IGFBP7, which encodes a secreted protein upregulated after loss of SDHB, shows decreased occupancy by H3K27me3 (histone 3 methylated on residue K27) in the absence of SDH
physiological function
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using the submitochondrial particles from the adult worms and L3 larvae of the parasitic nematode Ascaris suum, it is shown that reactive oxygen species are produced from the flavin adenine dinucleotide-binding site as well as the quinone binding site in the mitochondrial complex II
physiological function
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enzyme belongs to a system of electron transport phosphorylation in which formate functions as the donor and fumarate as the terminal acceptor. Menaquinone is an obligatory redox mediator of formate-fumarate reductase electron transport phosphorylation system
physiological function
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fumarate reductase, which is proficient in succinate oxidation, is able to functionally replace succinate-ubiquinone oxidoreductase in aerobic respiration when conditions are used to allow the expression of the frdABCD operon aerobically. Expression of plasmids which utilize the FRD promoter of the frdABCD operon fused to the sdhCDAB genes to drive expression shows that, under anaerobic growth conditions where fumarate is utilized as the terminal electron acceptor, succinate-ubiquinone oxidoreductase would function to support anaerobic growth of Escherichia coli
physiological function
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fumarate reduction by NADH is catalyzed by an electron transport chain consisting of NADH dehydrogenase NADH:menaquinone reductase, menaquinone, and succinate dehydrogenase operating in the reverse direction, i.e. menaquinol:fumarate reductase. In sdh or aro mutant strains, which lack succinate dehydrogenase or menaquinone, respectively, the activity of fumarate reduction by NADH is missing. The membrane fraction of a mutant lacking functional sdh genes catalyzes fumarate reduction by NADH or 2,3-dimethyl-1,4-naphthoquinol with less than 7% of the wild-type activities. In resting cells fumarate reduction requires glycerol or glucose as the electron donor, which presumably supply NADH for fumarate reduction
physiological function
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is involved in anaerobic respiration with fumarate as the terminal electron acceptor, and is part of an electron transport chain catalysing the oxidation of various donor substrates by fumarate
physiological function
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the enzyme is involved in aerobic metabolism as part of the citric acid cycle and of the aerobic respiratory chain
physiological function
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the enzyme is involved in aerobic metabolism as part of the citric acid cycle and of the aerobic respiratory chain
physiological function
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the enzyme is involved in anaerobic metabolism
physiological function
-
the enzyme is involved in anaerobic respiration with fumarate as the terminal electron acceptor, and is part of an electron transport chain catalysing the oxidation of various donor substrates by fumarate
physiological function
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the FrdD subunit has an essential role both in the interaction of the enzyme with reduced menaquinone and thus in anaerobic respiration with fumarate as electron acceptor, and in binding the enzyme to the membrane
physiological function
the QFR complex provides electron transport during anaerobic cell growth conditions. The transcription of the frdABCD operon responds to environmental as well as internal cell signals to modulate gene expression. The transcription is coupled to that of the succinate-ubiquinone oxidase, EC 1.3.5.1, overview
physiological function
the SQR complex provides electron transport during aerobic cell growth conditions. The transcription of the sdhCDAB operon responds to environmental as well as internal cell signals to modulate gene expression. The transcription is coupled to that of the menaquinol-fumarate oxidoreductase, EC 1.3.5.4, overview
physiological function
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succinate:quinone reductase serves as the respiratory complex II
physiological function
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succinate:ubiquinone oxidoreductase is part of the mitochondrial respiratory complex II
physiological function
the enzyme is involved in electron transfer via the respiratory chain
physiological function
the enzyme is part of the complex II, which in the anaerobic respiratory chain of the parasitic nematode Ascaris suum, couples the reduction of fumarate to the oxidation of rhodoquinol. Critical role of the low redox potential of rhodoquinol in the fumarate reduction of Ascaris suum complex II
physiological function
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a subunit MfrA mutant strain is less susceptible to H2O2 as the wildtype. The H2O2 concentration in the mutant cultures is significantly higher than that of wild-type. In the presence of H2O2, catalase activity and expression are lower in the mutant strain as compared to the wild-type. Exposure to H2O2 results in a significant decrease in total intracellular iron in the mutant strain, while the addition of iron to the growth medium mitigates H2O2 susceptibility and accumulation in the mutant. The mutant strain is significantly more persistent in RAW macrophages
physiological function
deletion of the sdh1 operon does not yield any growth phenotypes on succinate or other nonfermentable carbon sources
physiological function
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overexpression of SdhC and SdhD suppresses 1-(4-chlorophenyl)-benzo-2,5-quinone-induced inhibition of complex II activity, increase in mitochondrial levels of reactive oxygen species, and toxicity
physiological function
presence of the Sdh2 operon is essential for growth. Isoform Sdh2 is the generator of the membrane potential under hypoxia
physiological function
acetylation can participate in the modulation of the enzymatic activity of SDH, a key enzyme of the tricarboxylic acid cycle, along with the well-known mechanisms of inhibition by oxaloacetic acid, oxidative stress, or mutations in enzyme subunits, in maintaining the energy supply, membrane potential, and other functions of mitochondria
physiological function
in addition to its role in bioenergetics, QFR binds to the FliG subunit of the switch-motor of the bacterial flagellar rotor and promotes clockwise rotation of the flagellum, which is essential for chemotaxis
physiological function
quinol:fumarate reductase (QFR, FrdABCD) catalyzes the interconversion of fumarate and succinate at a covalently attached FAD within the FrdA subunit. The SdhE assembly factor enhances covalent flavinylation of complex II homologues, mechanism, overview. QFR catalyzes the reduction of fumarate (kcat = 250/s) at this flavin-based active site during anaerobic respiration with fumarate as the terminal electron acceptor. In this process, the two electrons for fumarate reduction derived from the oxidation of menaquinol in the membrane and the two protons are likely transferred from solvent via a proton shuttle pathway consisting of the FrdA-E245, FrdA-R248, and FrdA-R287 side chains located on the capping domain. QFR can also catalyze the reverse reaction, succinate oxidation, albeit with slower kinetics (kcatx02= 30/s) and poorer catalytic efficiency
physiological function
succinate dehydrogenase (SDH) is a protein complex that links the Krebs cycle to the electron transport system. It can produce significant amounts of superoxide and hydrogen peroxide (H2O2), kinetic mechanism and computational modelling including the major redox centers in the complex, namely FAD, three iron-sulfur clusters, and a transiently bound semiquinone, overview
physiological function
succinate dehydrogenase (SDH) is an inner mitochondrial membrane protein complex that links the Krebs cycle to the electron transport system. It can produce significant amounts of superoxide and hydrogen peroxide (H2O2), kinetic mechanism and computational modelling including the major redox centers in the complex, namely FAD, three iron-sulfur clusters, and a transiently bound semiquinone, detailed overview. Oxidation state transitions involve a one- or two-electron redox reaction, each being thermodynamically constrained. When the quinone reductase site is inhibited or the quinone pool is highly reduced, superoxide is generated primarily by the FAD. In addition, H2O2 production is only significant when the enzyme is fully reduced, and fumarate is absent. SDH significantly contributes to total mitochondrial ROS production
physiological function
succinate dehydrogenase (SDH) is an inner mitochondrial membrane protein complex that links the Krebs cycle to the electron transport system. It can produce significant amounts of superoxide and hydrogen peroxide (H2O2), kinetic mechanism and computational modelling including the major redox centers in the complex, namely FAD, three iron-sulfur clusters, and a transiently bound semiquinone, detailed overview. Oxidation state transitions involve a one- or two-electron redox reaction, each being thermodynamically constrained. When the quinone reductase site is inhibited or the quinone pool is highly reduced, superoxide is generated primarily by the FAD. In addition, H2O2 production is only significant when the enzyme is fully reduced, and fumarate is absent. SDH significantly contributes to total mitochondrial ROS production
physiological function
succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. Enzyme regulation can occur via transcription factors, post-transcriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview. In bacteria alteration of SDH expression by aerobiosis/anaerobiosis and various carbon sources is also implemented through transcriptional regulation. In this case fnr and arcA gene products both act to repress SDHC expression in response to oxygen. In Escherichia coli a EIICBGlc protein (the ptsG gene product) is identified, that is a component of the major glucose transport machinery known as phosphoenolpyruvate (PEP) phosphotransferase system (PTS), and a crucial mediator of the repression of the sdhCDAB operon in the presence of glucose. It acts via the transcription factor crp, which directly regulates expression of the sdhCDAB operon. The glucose repression of this operon occurs in a cAMP-dependent manner
physiological function
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succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. Enzyme regulation can occur via transcription factors, posttranscriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview. In bacteria alteration of SDH expression by aerobiosis/anaerobiosis and various carbon sources is also implemented through transcriptional regulation. In this case fnr and arcA gene products both act to repress SDHC expression in response to oxygen
physiological function
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succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. Enzyme regulation can occur via transcription factors, posttranscriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview. In bacteria alteration of SDH expression by aerobiosis/anaerobiosis and various carbon sources is also implemented through transcriptional regulation. In this case fnr and arcA gene products both act to repress SDHC expression in response to oxygen
physiological function
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succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. Enzyme regulation can occur via transcription factors, posttranscriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview. In bacteria alteration of SDH expression by aerobiosis/anaerobiosis and various carbon sources is also implemented through transcriptional regulation. In this case fnr and arcA gene products both act to repress SDHC expression in response to oxygen. In Neisseria meningitides low iron condition leads to high expression of NrrF. The latter is an sRNA that targets sdhCDAB transcript and promotes its degradation with the assistance of Hfq chaperone. The concentration of iron is sensed by Fur which represses the genes responsible for iron uptake with the assistance of ferrous iron as a corepressor
physiological function
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succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. Enzyme regulation can occur via transcription factors, posttranscriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview. In bacteria alteration of SDH expression by aerobiosis/anaerobiosis and various carbon sources is also implemented through transcriptional regulation. In this case, fnr and arcA gene products both act to repress SDHC expression in response to oxygen
physiological function
succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. Enzyme regulation can occur via transcription factors, posttranscriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview. In yeast, glucose represses the transcription of SDH2 (SDHB homologue) by a mechanism in which the upstream promoter sequence of SDHB containing four regulatory elements is shown to interact with the HAP2/3/4 transcription activator complex. Maximum expression of SDH1 (SDHA homologue) and SDH3 (SDHC homologue) require the same transcription activator. Accordingly, the expression of SDH1 and SDH3 is enhanced 5 times more strongly on galactose than on glucose. Likewise, an increase in the abundance of SDH4 (SDHD homologue) mRNA observed in media containing galactose rather than glucose. Therefore it seems that the same transcription activator complex regulates the transcription of all 4 genes encoding subunits of SDH. The 5'-untranslated region (5' UTR) of the SDH2 mRNA contains a major determinant which controls its differential turnover in media containing glycerol versus glucose. Furthermore, the 5' exonuclease encoded by the XRN1 gene is necessary for the rapid degradation of the SDH1 and SDH2 mRNAs in the presence of glucose
physiological function
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succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. SDH function is tailored in different cell types to meet the energy demands, SDH function is differently regulated in distinct cell types. Enzyme regulation can occur via transcription factors, post-transcriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview. In Brassica hexaploids transcriptions of SDH genes are activated by long non-coding RNAs possibly to stimulate energy production via TCA cycle
physiological function
succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. SDH function is tailored in different cell types to meet the energy demands, SDH function is differently regulated in distinct cell types. Enzyme regulation can occur via transcription factors, post-transcriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview. In human cells, the nuclear respiratory factor-1 (NRF-1) initially is the primary transcriptional regulator of mitochondrial biogenesis. NRF-1 also induces SDH expression through binding to the gene promoters of SDHA and SDHD in the aerobic cardiomyocyte. Low levels of NFR-1 downregulate SDHA and thereby SDH complex expression. This stabilizes HIF-1 and promotes its nuclear translocation and high expression of glucose transporters and heme oxygenase-1. Transcription of the genes encoding SDH subunits (particularly SDHB) of human myoblast cells requires NRF-1 and NRF-2 transcription factors. Certain levels of desuccinylase SIRT5 are required for physiological activity of SDH and any imbalance i.e. either too low or too high levels, may influence SDH activity. Direct effectors are either deactivators such as oxaloacetate or activators such as substrates, anions, reduced quinone, ATP, and reduction. The interaction between SDH and oxaloacetate renders the enzyme inactive, while the interaction between the activator and enzyme prevent such interaction with oxaloacetate
physiological function
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succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. SDH function is tailored in different cell types to meet the energy demands, SDH function is differently regulated in distinct cell types. Enzyme regulation can occur via transcription factors, posttranscriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview
physiological function
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succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. SDH function is tailored in different cell types to meet the energy demands, SDH function is differently regulated in distinct cell types. Enzyme regulation can occur via transcription factors, posttranscriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview
physiological function
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succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. SDH function is tailored in different cell types to meet the energy demands, SDH function is differently regulated in distinct cell types. Enzyme regulation can occur via transcription factors, posttranscriptional regulators and modifiers, e.g. through phosphorylation, deacetylation, succinylation, propionylation, or direct effection, overview
physiological function
succinate:quinone oxidoreductase (SQR) is a multisubunit membrane-associated enzyme found in the cytoplasm of bacteria and in the matrix of mitochondria (where it is commonly termed complex II). The enzyme is central to cellular metabolism and energy conversion, contributing to the tricarboxylic acid cycle and the electron transport chain. It catalyzes the oxidation of succinate to fumarate, which is coupled to electron transfer through flavin adenine dinucleotide (FAD) and three Fe-S clusters, resulting in the reduction of the electron carrier ubiquinone to ubiquinol. Succinate:quinone oxidoreductase (SQR) functions in energy metabolism, coupling the tricarboxylic acid cycle and electron transport chain in bacteria and mitochondria
physiological function
Megalodesulfovibrio gigas
the membrane-embedded quinol:fumarate reductase (QFR) in anaerobic bacteria catalyzes the reduction of fumarate to succinate by quinol in the anaerobic respiratory chain
physiological function
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the enzyme is involved in electron transfer via the respiratory chain
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physiological function
Megalodesulfovibrio gigas DSM 1382
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the membrane-embedded quinol:fumarate reductase (QFR) in anaerobic bacteria catalyzes the reduction of fumarate to succinate by quinol in the anaerobic respiratory chain
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physiological function
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deletion of the sdh1 operon does not yield any growth phenotypes on succinate or other nonfermentable carbon sources
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physiological function
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presence of the Sdh2 operon is essential for growth. Isoform Sdh2 is the generator of the membrane potential under hypoxia
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physiological function
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succinate dehydrogenase (SDH) is a protein complex that links the Krebs cycle to the electron transport system. It can produce significant amounts of superoxide and hydrogen peroxide (H2O2), kinetic mechanism and computational modelling including the major redox centers in the complex, namely FAD, three iron-sulfur clusters, and a transiently bound semiquinone, overview
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physiological function
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acetylation can participate in the modulation of the enzymatic activity of SDH, a key enzyme of the tricarboxylic acid cycle, along with the well-known mechanisms of inhibition by oxaloacetic acid, oxidative stress, or mutations in enzyme subunits, in maintaining the energy supply, membrane potential, and other functions of mitochondria
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physiological function
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succinate dehydrogenase (SDH) is a protein complex that links the Krebs cycle to the electron transport system. It can produce significant amounts of superoxide and hydrogen peroxide (H2O2), kinetic mechanism and computational modelling including the major redox centers in the complex, namely FAD, three iron-sulfur clusters, and a transiently bound semiquinone, overview
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physiological function
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succinate:quinone reductase serves as the respiratory complex II
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additional information
enzyme structure-function relationship, overview
additional information
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enzyme structure-function relationship, overview
additional information
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the E-pathway of transmembrane proton transfer is essential for catalysis by the diheme-containing quinol:fumarate reductase, molecular dynamics simulations, overview. The redox state of heme groups has a crucial effect on the connectivity patterns of mobile internal water molecules that can transiently support proton transfer from the bD-C-propionate to Glu-C180. The short H-bonding paths formed in the reduced states can lead to high proton conduction rates. The bD-C-propionate group is the branching point connecting proton transfer to the E-pathway from the quinol-oxidation site via interactions with the heme bD ligand His-C44, essential functional role of His-C44, hydrogen-bonded networks between the bD-C-propionate and Glu180, overview
additional information
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the E-pathway of transmembrane proton transfer is essential for catalysis by the diheme-containing quinol:fumarate reductase, molecular dynamics simulations, overview. The redox state of heme groups has a crucial effect on the connectivity patterns of mobile internal water molecules that can transiently support proton transfer from the bD-C-propionate to Glu-C180. The short H-bonding paths formed in the reduced states can lead to high proton conduction rates. The bD-C-propionate group is the branching point connecting proton transfer to the E-pathway from the quinol-oxidation site via interactions with the heme bD ligand His-C44, essential functional role of His-C44, hydrogen-bonded networks between the bD-C-propionate and Glu180, overview
additional information
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the E-pathway of transmembrane proton transfer is essential for catalysis by the diheme-containing quinol:fumarate reductase, molecular dynamics simulations, overview. The redox state of heme groups has a crucial effect on the connectivity patterns of mobile internal water molecules that can transiently support proton transfer from the bD-C-propionate to Glu-C180. The short H-bonding paths formed in the reduced states can lead to high proton conduction rates. The bD-C-propionate group is the branching point connecting proton transfer to the E-pathway from the quinol-oxidation site via interactions with the heme bD ligand His-C44, essential functional role of His-C44, hydrogen-bonded networks between the bD-C-propionate and Glu180, overview
additional information
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the membrane part of the enzyme is functionally connected to the active site, structure-function relationship, overview
additional information
FrdAR287 is essential for catalytic protonation/deprotonation of fumarate/succinate, an intriguing mechanism for substrate control of capping domain position is via the charge on the dicarboxylate affecting the pKa of FrdAR287. Ligand control of domain position suggests a mechanism for ingress and egress of substrate facilitated by the changes in the locations of active site residues
additional information
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FrdAR287 is essential for catalytic protonation/deprotonation of fumarate/succinate, an intriguing mechanism for substrate control of capping domain position is via the charge on the dicarboxylate affecting the pKa of FrdAR287. Ligand control of domain position suggests a mechanism for ingress and egress of substrate facilitated by the changes in the locations of active site residues
additional information
Megalodesulfovibrio gigas
quinol:fumarate reductase (QFR) is an integral membrane protein with three subunits: a flavoprotein (subunit A), an iron-sulphur protein (subunit B), and a membrane-embedded subunit (subunit C)
additional information
SDH complex structure and assembly, detailed overview. Detailed analysis of some proteins that are required for the assembly of SDH e.g. Tcm62p, Flx1, Sdh6 (in yeast), SDH7 (in yeast), and Sdh5 (in yeast). Tcm62 most likely has a chaperone function for SDH, while Sdh5 plays a role in SDH1 flavination. The current model of complex II (succinate dehydrogenase) assembly: Sdh5 bound to Sdh1 facilitates flavination of Sdh1. Sdh5 is then released, while Sdh8 chaperone binds the flavinated Sdh1 to facilitate the dimerization of Sdh1 and Sdh2. Sdh6 and Sdh7 assist in either insertion or retention of [Fe-S] clusters within Sdh2. Sdh2 then forms a dimer with Sdh1, while Sdh6/Sdh7 and Sdh8 are released from Sdh2 and Sdh1, respectively. The dimer is subsequently integrated into the membrane where Sdh3-Sdh4 dimer containing a heme b is formed. There is not much information regarding the formation of Sdh3-Sdh4 dimer. Role of SDH2 in flavination. SDHAF3 together with SDHAF1 is asserted as factors required for maturation of Sdh2/SDHB
additional information
SDH complex structure and assembly, detailed overview. The SDHA subunit is a flavoprotein containing a covalently bound FAD cofactor and the binding site for dicarboxylates (e.g. succinate). SDHB is an iron-sulfur cluster protein containing three Fe-S clusters. SDHA and SDHB make up the catalytic domain. They extend out into the matrix and constitute the hydrophilic head. SDHC and SDHD subunits are alpha-helical transmembrane proteins which ligate a single heme between them. Detailed analysis of some proteins that are required for the assembly of SDH e.g. Tcm62p, Flx1, SDHAF1 or LYRM8, SDHAF3, and SDHAF2. Tcm62 most likely has a chaperone function for SDH. Role of SDHB in flavination. SDHAF3 together with SDHAF1 is asserted as factors required for maturation of Sdh2/SDHB
additional information
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SDH complex structure and assembly, detailed overview. The SDHA subunit is a flavoprotein containing a covalently bound FAD cofactor and the binding site for dicarboxylates (e.g. succinate). SDHB is an iron-sulfur cluster protein containing three Fe-S clusters. SDHA and SDHB make up the catalytic domain. They extend out into the matrix and constitute the hydrophilic head. SDHC and SDHD subunits are alpha-helical transmembrane proteins which ligate a single heme between them. Detailed analysis of some proteins that are required for the assembly of SDH e.g. Tcm62p, Flx1, SDHAF1 or LYRM8, SDHAF3, and SDHAF2. Tcm62 most likely has a chaperone function for SDH. Role of SDHB in flavination. SDHAF3 together with SDHAF1 is asserted as factors required for maturation of Sdh2/SDHB
additional information
succinate dehydrogenase (SDH) can produce significant amounts of superoxide and hydrogen peroxide (H2O2), which hinders the development of next-generation antioxidant therapies targeting mitochondria
additional information
succinate dehydrogenase (SDH) can produce significant amounts of superoxide and hydrogen peroxide (H2O2), which hinders the development of next-generation antioxidant therapies targeting mitochondria
additional information
the membrane-anchored SdhF is a subunit of the enzyme complex II (Sdh2). The 3 kDa SdhF forms a single transmembrane helix, and this helix plays a role in blocking the canonically proximal quinone-binding site. Location and interaction of SdhF subunit in Sdh2 protein. Two distal quinone-binding sites with bound quinones are identified, one distal binding site is formed by neighboring subunits of the complex. Major redox centers in the complex are FAD, three iron-sulfur clusters, and a transiently bound semiquinone. The purified recombinant Sdh2 is a functioning complex that couples succinate oxidation to menadione reduction. Enzyme structure analysis, overview
additional information
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the membrane-anchored SdhF is a subunit of the enzyme complex II (Sdh2). The 3 kDa SdhF forms a single transmembrane helix, and this helix plays a role in blocking the canonically proximal quinone-binding site. Location and interaction of SdhF subunit in Sdh2 protein. Two distal quinone-binding sites with bound quinones are identified, one distal binding site is formed by neighboring subunits of the complex. Major redox centers in the complex are FAD, three iron-sulfur clusters, and a transiently bound semiquinone. The purified recombinant Sdh2 is a functioning complex that couples succinate oxidation to menadione reduction. Enzyme structure analysis, overview
additional information
Megalodesulfovibrio gigas DSM 1382
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quinol:fumarate reductase (QFR) is an integral membrane protein with three subunits: a flavoprotein (subunit A), an iron-sulphur protein (subunit B), and a membrane-embedded subunit (subunit C)
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additional information
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the membrane-anchored SdhF is a subunit of the enzyme complex II (Sdh2). The 3 kDa SdhF forms a single transmembrane helix, and this helix plays a role in blocking the canonically proximal quinone-binding site. Location and interaction of SdhF subunit in Sdh2 protein. Two distal quinone-binding sites with bound quinones are identified, one distal binding site is formed by neighboring subunits of the complex. Major redox centers in the complex are FAD, three iron-sulfur clusters, and a transiently bound semiquinone. The purified recombinant Sdh2 is a functioning complex that couples succinate oxidation to menadione reduction. Enzyme structure analysis, overview
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additional information
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the membrane-anchored SdhF is a subunit of the enzyme complex II (Sdh2). The 3 kDa SdhF forms a single transmembrane helix, and this helix plays a role in blocking the canonically proximal quinone-binding site. Location and interaction of SdhF subunit in Sdh2 protein. Two distal quinone-binding sites with bound quinones are identified, one distal binding site is formed by neighboring subunits of the complex. Major redox centers in the complex are FAD, three iron-sulfur clusters, and a transiently bound semiquinone. The purified recombinant Sdh2 is a functioning complex that couples succinate oxidation to menadione reduction. Enzyme structure analysis, overview
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additional information
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the membrane part of the enzyme is functionally connected to the active site, structure-function relationship, overview
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