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evolution
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NAD+-dependent, NADP+-dependent and dual-specificity GDHs, EC 1.4.1.2-1.4.1.4 are closely related and a few site-directed mutations can reverse specificity, overview. Specificity for NAD+ or for NADP+ has probably emerged repeatedly during evolution, using different structural solutions on different occasions. an acidic P7 residue usually hydrogen bonds to the 2'- and 3'-hydroxyls, may permit binding of NAD+ only, NADP+ only, or in higher animals both
evolution
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NAD+-dependent, NADP+-dependent and dual-specificity GDHs, EC 1.4.1.2-1.4.1.4 are closely related and a few site-directed mutations can reverse specificity, overview. Specificity for NAD+ or for NADP+ has probably emerged repeatedly during evolution, using different structural solutions on different occasions. an acidic P7 residue usually hydrogen bonds to the 2'- and 3'-hydroxyls, may permit binding of NAD+ only, NADP+ only, or in higher animals both
evolution
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the enzyme belongs to the family of amino acid dehydrogenases
evolution
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the enzyme belongs to the family of amino acid dehydrogenases
evolution
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the enzyme belongs to the family of amino acid dehydrogenases
evolution
BpNADGDH gives over 65% identity scores with fungal NAD-dependent GDHs
evolution
GDHs are members of a superfamily of ELFV (Glu/Leu/Phe/Val) amino acid dehydrogenases and are subdivided into three subclasses, based on coenzyme specificity: NAD+-specific, NAD+/NADP+ dual-specific, and NADP+-specific. The mitochondrial AtGDH1 isozyme from Arabidopsis thaliana is NAD+-specific. Arabidopsis thaliana expresses three GDH isozymes (AtGDH1-3) targeted to mitochondria, of which AtGDH2 has an extra EF-hand motif and is stimulated by calcium, while AtGDH1's sensitivity to calcium is negligible. In vivo the AtGDH1-3 enzymes form homo- and heterohexamers of varied composition. Phylogenetic analysis of GDHs in plants. Plants have distinct isozymes of GDH that are either NAD or NADP-specific. NAD-specific GDHs are localized in mitochondria, whereas NADP-specific GDHs exist in chloroplasts. The sequence region 257-264 in AtGDH1 and AtGDH2, which directly precedes the EF-hand motif in AtGDH2 (residues 265-277), is the most altered region of AtGDH2 in comparison with AtGDH1
evolution
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in 39 wild isolates of Lactococcus lactis from raw milk cheeses, only 25% of the isolates are glutamate dehydrogenase positive with NAD+ as the preferred cofactor. Lactococcus lactis IFPL953 shows the highest NAD-GDH activity
evolution
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in 39 wild isolates of Lactococcus lactis from raw milk cheeses, only 25% of the isolates are glutamate dehydrogenase positive with NAD+ as the preferred cofactor. Lactococcus lactis IFPL953 shows the highest NAD-GDH activity
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malfunction
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a gdh1-2-3 triple mutant exhibits major differences to the wild-type in gene transcription and metabolite concentrations, and these differences appear to originate in the roots, metabolic profile of the gdh1-2-3 triple mutant, overview
malfunction
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when one or two of the three root isoenzymes are missing from the mutants, the remaining isoenzymes compensate for this deficiency
malfunction
the disruption of GDH2 was not deleterious to glutamate homeostasis. Mutant gdh2DELTA cells present wild-type growth and do not display any deficiencies due to glutamate homeostasis impairment neither under glucose nor under non-fermentable carbon sources. Deletion of GDH2 gene in a gdh3DELTA background increases the resistance under thermal or oxidative stress by decreasing ROS accumulation. The apoptosis is suppressed by GDH2 deletion through the elevated levels of glutamate and glutathione present in the double mutant. Under the tested conditions, deletion of GDH2 compensates the depletion of intracellular glutamate and glutathione (GSH) followed by stress-induced apoptotic cell death reinforcing further the idea that Gdh2p is responsible only for glutamate catabolism and not its production
malfunction
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the disruption of GDH2 was not deleterious to glutamate homeostasis. Mutant gdh2DELTA cells present wild-type growth and do not display any deficiencies due to glutamate homeostasis impairment neither under glucose nor under non-fermentable carbon sources. Deletion of GDH2 gene in a gdh3DELTA background increases the resistance under thermal or oxidative stress by decreasing ROS accumulation. The apoptosis is suppressed by GDH2 deletion through the elevated levels of glutamate and glutathione present in the double mutant. Under the tested conditions, deletion of GDH2 compensates the depletion of intracellular glutamate and glutathione (GSH) followed by stress-induced apoptotic cell death reinforcing further the idea that Gdh2p is responsible only for glutamate catabolism and not its production
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metabolism
NAD+-GDH plays an important role in nitrogen assimilation rather than glutamate catabolism, and is involved in the additional nitrogen assimilatory pathway via glutamate dehydrogenase, GDH. The specific activity of the deaminating NAD+-GDH reaction is mostly independent of nitrogen availability, overview, overview
metabolism
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together with glutamine synthetase, the glutamate synthase, i.e. enzyme GOGAT, EC 1.4.1.14, offers the same net reaction as GDH, but with a much lower Km for ammonia, and driven by the splitting of ATP
metabolism
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together with glutamine synthetase, the glutamate synthase, i.e. enzyme GOGAT, EC 1.4.1.14, offers the same net reaction as GDH, but with a much lower Km for ammonia, and driven by the splitting of ATP
metabolism
GDH contributes to Glu homeostasis and plays a significant role at the junction of carbon and nitrogen assimilation pathways
metabolism
through the enzymatic activity of Gdh2p the breakdown of glutamate provides adequate levels of ammonia in yeast cells. The catabolism of glutamate via the NAD-GDH activity is the major pathway of ammonia generation in vivo. Synthesis of glutamate occurs through the action of NADP-GDH (encoded by GDH1 and GDH3 genes, EC 1.4.1.4). NAD-GDH activity (encoded by GDH2) is responsible for glutamate degradation and release of ammonium and 2-oxoglutarate. The role of GDH1 and GDH2 is contradictory when investigated in yeast strains under cold-growth conditions
metabolism
YALI0F17820g (ylGDH, EC 1.4.1.4) encodes a NADP-dependent GDH whereas YALI0E09603g (ylGDH2, EC 1.4.1.2) encodes a NAD-dependent GDH enzyme. The activity encoded by these two genes accounts for all measurable GDH activity in Yarrowia lipolytica. Levels of the two enzyme activities are comparable during logarithmic growth on rich medium, but the NADP-ylGDH1p enzyme activity is most highly expressed in stationary and nitrogen starved cells by 3fold to 12fold compared to NAD-ylGDH2p. Replacement of ammonia with glutamate causes a decrease in NADP-ylGdh1p activity, whereas NAD-ylGdh2p activity is increased. When glutamate is both carbon and nitrogen sources, the activity of NAD-ylGDH2p becomes dominant up to 18fold compared with that of NADP-ylGDH1p. ylGDH1 and ylGDH2 are functionally not interchangeable
metabolism
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YALI0F17820g (ylGDH, EC 1.4.1.4) encodes a NADP-dependent GDH whereas YALI0E09603g (ylGDH2, EC 1.4.1.2) encodes a NAD-dependent GDH enzyme. The activity encoded by these two genes accounts for all measurable GDH activity in Yarrowia lipolytica. Levels of the two enzyme activities are comparable during logarithmic growth on rich medium, but the NADP-ylGDH1p enzyme activity is most highly expressed in stationary and nitrogen starved cells by 3fold to 12fold compared to NAD-ylGDH2p. Replacement of ammonia with glutamate causes a decrease in NADP-ylGdh1p activity, whereas NAD-ylGdh2p activity is increased. When glutamate is both carbon and nitrogen sources, the activity of NAD-ylGDH2p becomes dominant up to 18fold compared with that of NADP-ylGDH1p. ylGDH1 and ylGDH2 are functionally not interchangeable
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metabolism
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through the enzymatic activity of Gdh2p the breakdown of glutamate provides adequate levels of ammonia in yeast cells. The catabolism of glutamate via the NAD-GDH activity is the major pathway of ammonia generation in vivo. Synthesis of glutamate occurs through the action of NADP-GDH (encoded by GDH1 and GDH3 genes, EC 1.4.1.4). NAD-GDH activity (encoded by GDH2) is responsible for glutamate degradation and release of ammonium and 2-oxoglutarate. The role of GDH1 and GDH2 is contradictory when investigated in yeast strains under cold-growth conditions
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physiological function
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a quantitative genetic study for elucidating the contribution of glutamine synthetase, glutamate dehydrogenase and other nitrogen-related physiological traits to the agronomic performance of common wheat is performed. A total of 148 quantitative trait loci are detected, 26 are detected for GDH activity spread over 13 chromosomes. A coincidence between a quantitative trait loci for GDH activity and a gene encoding GDH is also found on chromosome 2B
physiological function
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GDH enzymes of 19 Streptococcus suis serotype 2 strains, consisting of 18 swine isolates and 1 human clinical isolate from a geographically varied collection, are analyzed by activity staining on a nondenaturing gel. DNA sequences contain base pair differences, but most are silent. Cluster analysis of the deduced amino acid sequences separated the isolates into three groups (ETI, ETII, ETIII). Gene exchange studies results in the change of ETI to ETII and vice versa. A spectrophotometric activity assay for GDH do not show significant differences between the groups
physiological function
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glucose deprivation in SF-188 cells results in an enhanced GDH activity. This results from the loss of glycolysis. Inhibition of Akt signaling, which facilitates glycolysis, increases GDH activity whereas overexpression of Akt suppresses it. Suppression of GDH activity with RNA interference or an inhibitor shows that the enzyme is dispensable in cells able to metabolize glucose but is required for cells to survive impairments of glycolysis brought about by glucose deprivation, 2-deoxyglucose, or Akt inhibition. Inhibition of GDH converts these glutamine-addicted SF-188 cells to glucose-addicted cells
physiological function
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sucrose starvation of lupine embryos leads to a rapid increase in the specific activity of GDH, immunoreactive beta-polypeptide and it is accompanied by appearance of new cathodal isoforms of enzyme, suggesting that isoenzymes induced in lupine embryos by sucrose starvation combine into GDH hexamers with the predominance of beta-GDH subunits synthetized under GDH1 gene control, treatment of cultivated embryos with 0.01 mM Cd2+ or Pb2+ results in ammonium accumulation in the tissues, accompanied by an increase in anabolic activity of GDH and activity of anodal isoenzymes
physiological function
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transgenic mice, betaGlud1-/-, are generated bearing a beta-cell-specific GDH deletion. In situ pancreatic perfusion reveals that glucose-stimulated insulin secretion is reduced by 37% in transgenic mice. Isolated islets with either constitutive or acute adenovirus-mediated knock-out of GDH show a 49 and 38% reduction in glucose-induced insulin release, respectively. Adenovirus-mediated re-expression of GDH in transgenic mice fully restores glucose-induced insulin release. In transgenic mice reduced secretory capacity results in lower plasma insulin levels in response to both feeding and glucose load, while body weight gain is preserved
physiological function
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transgenic tobacco plants overexpressing the two genes encoding the enzyme are generated. Using an in vivo real time 15 N-nuclear magnetic resonance (NMR) spectroscopy approach it is shown that, when the two GDH genes are overexpressed individually or simultaneously, the transgenic plant leaves do not synthesize glutamate in the presence of NH4+ when glutamine synthetase is inhibited. When the two GDH unlabeled substrates ammonium and glutamate are provided simultaneously with either (15N) glutamate or 15NH4+ respectively, it is found that the ammonium released from the deamination of glutamate is reassimilated by the enzyme glutamine synthase, suggesting the occurrence of a futile cycle recycling both ammonium and glutamate
physiological function
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complex regulatory behaviour in mammalian GDH, involving negative co-operativity in coenzyme binding. Main heterotropic regulators are ADP and GTP, and ADP is a fragment of the coenzyme. NAD(H) mediates homotropic interaction via heterotropic sites or conversely, ADP uses homotropic coenzyme sites
physiological function
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complex regulatory behaviour in mammalian GDH, involving negative co-operativity in coenzyme binding. Main heterotropic regulators are ADP and GTP, and ADP is a fragment of the coenzyme. NAD(H) mediates homotropic interaction via heterotropic sites or conversely, ADP uses homotropic coenzyme sites
physiological function
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CsGDH lacks the regulation by ADP and GTP seen in bovine GDH
physiological function
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Gdh2p plays an evident role during aerobic glutamate metabolism
physiological function
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isozyme GDH7 does not support net amination in vivo and the increase in GDH7 activity might be a response to oxidative stress during protoplast isolation
physiological function
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the main physiological function of NADH-GDH is to provide 2-oxoglutarate for the tricarboxylic acid cycle. Differences in key metabolites of the tricarboxylic acid cycle in the triple mutant versus the wild-type indicate that, through metabolic processes operating mainly in roots, there is a strong impact on amino acid accumulation, in particular alanine, gamma-aminobutyrate, and aspartate in both roots and leaves, phenotypes, overview
physiological function
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a gene disruption mutant fails to produce and secrete glutamate dehydrogenase. In tryptose yeast extract medium, the gluD mutant grows slower than the parent strain. The mutant displys higher sensitivity to H2O2
physiological function
a high-copy number of the GDH2-encoded NADH-specific glutamate dehydrogenase gene stimulates growth at 15°C, while overexpression of NADPH-specific GDH1 has detrimental effects. Total cellular NAD levels are a limiting factor for growth at low temperature in Saccharomyces cerevisiae. Increasing NADH oxidation by overexpression of GDH2 may help to avoid perturbations in the redox metabolism induced by a higher fermentative/oxidative balance at low temperature. Overexpression of GDH2 increases notably the cold growth in the wine yeast strain QA23 in both standard growth medium and synthetic grape must
physiological function
enzyme coordinates metabolism with cell division. Enzymatically active NAD-dependent glutamate dehydrogenase GdhZ directly interferes with FtsZ polymerization by stimulating its GTPase activity, and oxidoreductase-like KidO bound to NADH destabilizes lateral interactions between FtsZ protofilaments. Both GdhZ and KidO share the same regulatory network to concomitantly stimulate the rapid disassembly of the Z-ring, necessary for the subsequent release of progeny cells
physiological function
gene knockout decreases the growth sevenfold and initiates the undecylprodigiosin production in complex Difco nutrient media. With glucose supplementation, the growth difference of the mutant disappears, and significantly increased actinorhodin and undecylprodigiosin biosynthesis can be obtained by limiting the glucose content (0.5 to 1.0%, w/v)
physiological function
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presence of GDH is required for the utilization of glutamate as a major carbon source and to sustain Mycobacterium bovis BCG during infection of both murine RAW 264.7 and bone-marrow derived and macrophages. Inactivation of Gdh increases sensitivity to low pH stress and nitrosative stress
physiological function
silencing of all the endogenous GDH isoform genes leads to a dramatic decrease in total GDH activity but not to any clear morphological or metabolic phenotype in leaves or green fruit. Red fruit on the transgenic plants show markedly reduced levels of Glu and a large increase in aspartate, glucose and fructose content in comparison to wild-type fruit
physiological function
gene YALI0F17820g (GDH1) encodes a NADP-dependent GDH whereas YALI0E09603g (GDH2) encodes a NAD-dependent GDH enzyme. The activity encoded by these two genes accounts for all measurable GDH activity in Yarrowia lipolytica. NAD-Gdh2 plays a role in nitrogen and carbon utilization from glutamate. GDH1 and GDH2 are not interchangeable
physiological function
glutamate dehydrogenase (GDH) releases ammonia in a reversible NAD(P)+-dependent oxidative deamination of glutamate that yields 2-oxoglutarate (2OG). Plants have distinct isozymes of GDH that are either NAD or NADP-specific. NAD-specific GDHs are localized in mitochondria, whereas NADP-specific GDHs exist in chloroplasts
physiological function
glutamate dehydrogenases (GDHs) are fundamental to cellular nitrogen and energy balance. NAD-ylGdh2p plays a role in nitrogen and carbon utilization from glutamate. Glutamate dehydrogenase (GDH) activity in gdh-null Saccharomyces cerevisiae mutant cells is restored by introduction of YALI0F17820g (ylGDH1, EC 1.4.1.4) or YALI0E09603g (ylGDH2) from Yarrowia lipolytica
physiological function
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in practical water restoration by aquatic plants, the alternative pathway of GDH is more important than the pathway catalyzed by GS in determining the tolerance of submerged macrophytes to high ammonium concentration. Both NADH-dependent and NADPH-dependent GDH (EC 1.4.1.4) show species-dependent variation, in the ammonium-tolerant species, Myriophyllum spicatum, there is a dose-response curve (from 49.46 to 132.99 nmol/min/mg protein for NADH-dependent GDH and 28.98 to 58.67 nmol/min/mg protein for NADPH-GDH), but in the ammonium-sensitive species, Potamogeton lucens, there is little change in activity
physiological function
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in practical water restoration by aquatic plants, the alternative pathway of GDH is more important than the pathway catalyzed by GS in determining the tolerance of submerged macrophytes to high ammonium concentration. Both NADH-dependent and NADPH-dependent GDH (EC 1.4.1.4) show species-dependent variation, in the ammonium-tolerant species, Myriophyllum spicatum, there is a dose-response curve (from 49.46 to 132.99 nmol/min/mg protein for NADH-dependent GDH and 28.98 to 58.67 nmol/min/mg protein for NADPH-GDH), but in the ammonium-sensitive species, Potamogeton lucens, there is little change in activity
physiological function
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the activity of glutamate dehydrogenase in the ammonium-tolerant species Myriophyllum spicatum leaves increases 169% for NADH-dependent GDH and 103% for NADPH-dependent GDH with the [NH4+-N] increasing from 0 to 100 mg/l, performing a dose-response curve while glutamine synthetase activity slightly changes
physiological function
the gdh2/gdh2 mutant is unable to grow on either arginine or proline as a sole carbon and nitrogen source. There is no obvious difference in hyphal development between the wild-type (parental) and the mutant strains when cultured in minimum mineral medium or under other hyphae-inducing conditions. When the gdh2/gdh2 mutant utilizes glucose as the sole carbon source, most of the intracellular metabolites are found at lower concentrations than in the wild-type strain except for cysteine, malonate, nicotinate, 9-heptadecenoate, and 2-phosphoenolpyruvate
physiological function
the NAD-GDH activity in yeast is encoded by GDH2 gene and catalyzes the oxidative deamination of glutamate to 2-oxoglutarate and ammonium. Yeast cells lacking GDH1 can use GDH2 to promote glutamate biosynthesis using ammonia as sole nitrogen source. Role of the GDH path in ROS-mediated apoptosis. GDH2 genetically interacts with GDH3 (EC 1.4.1.4) and controls stress-induced apoptosis. Role of GDH2 in glutamate homeostasis. GDH2 genetically interacts with GDH3 and controls stress-induced apoptosis
physiological function
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a gene disruption mutant fails to produce and secrete glutamate dehydrogenase. In tryptose yeast extract medium, the gluD mutant grows slower than the parent strain. The mutant displys higher sensitivity to H2O2
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physiological function
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gene YALI0F17820g (GDH1) encodes a NADP-dependent GDH whereas YALI0E09603g (GDH2) encodes a NAD-dependent GDH enzyme. The activity encoded by these two genes accounts for all measurable GDH activity in Yarrowia lipolytica. NAD-Gdh2 plays a role in nitrogen and carbon utilization from glutamate. GDH1 and GDH2 are not interchangeable
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physiological function
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glutamate dehydrogenases (GDHs) are fundamental to cellular nitrogen and energy balance. NAD-ylGdh2p plays a role in nitrogen and carbon utilization from glutamate. Glutamate dehydrogenase (GDH) activity in gdh-null Saccharomyces cerevisiae mutant cells is restored by introduction of YALI0F17820g (ylGDH1, EC 1.4.1.4) or YALI0E09603g (ylGDH2) from Yarrowia lipolytica
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physiological function
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the gdh2/gdh2 mutant is unable to grow on either arginine or proline as a sole carbon and nitrogen source. There is no obvious difference in hyphal development between the wild-type (parental) and the mutant strains when cultured in minimum mineral medium or under other hyphae-inducing conditions. When the gdh2/gdh2 mutant utilizes glucose as the sole carbon source, most of the intracellular metabolites are found at lower concentrations than in the wild-type strain except for cysteine, malonate, nicotinate, 9-heptadecenoate, and 2-phosphoenolpyruvate
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physiological function
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gene knockout decreases the growth sevenfold and initiates the undecylprodigiosin production in complex Difco nutrient media. With glucose supplementation, the growth difference of the mutant disappears, and significantly increased actinorhodin and undecylprodigiosin biosynthesis can be obtained by limiting the glucose content (0.5 to 1.0%, w/v)
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physiological function
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the NAD-GDH activity in yeast is encoded by GDH2 gene and catalyzes the oxidative deamination of glutamate to 2-oxoglutarate and ammonium. Yeast cells lacking GDH1 can use GDH2 to promote glutamate biosynthesis using ammonia as sole nitrogen source. Role of the GDH path in ROS-mediated apoptosis. GDH2 genetically interacts with GDH3 (EC 1.4.1.4) and controls stress-induced apoptosis. Role of GDH2 in glutamate homeostasis. GDH2 genetically interacts with GDH3 and controls stress-induced apoptosis
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additional information
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at position 242, P6 of the core fingerprint, where NAD+- and NADP+-dependent enzymes normally have Gly or Ala, respectively, clostridial GDH already has Ala. Replacement with Gly produced negligible shift in coenzyme specificity
additional information
each polypeptide consists of an N-terminal substrate-binding (domain I) followed by a C-terminal cofactor-binding segment (domain II). The reaction takes place at the junction of the two domains, which move as rigid bodies and are presumed to narrow the cleft during catalysis. Critical glutamate at the P7 position of the core fingerprint with a role in NAD+ binding, mutational and isothermal titration calorimetry studies, overview
additional information
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each polypeptide consists of an N-terminal substrate-binding (domain I) followed by a C-terminal cofactor-binding segment (domain II). The reaction takes place at the junction of the two domains, which move as rigid bodies and are presumed to narrow the cleft during catalysis. Critical glutamate at the P7 position of the core fingerprint with a role in NAD+ binding, mutational and isothermal titration calorimetry studies, overview
additional information
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GDH from Peptoniphilus asaccharolyticus obeys the rules with Gly at P6 and Glu at P7
additional information
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in clostridial GDH, which shows a remarkable discrimination (20000-80000fold) in favour of NAD+, the P6 residue, which should be Gly, is in fact Ala. Not only this, but the critical P7 residue is Gly instead of Asp or Glu
additional information
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structure-activity relationship, modeling, comparison to other hyperthermophilic enzymes from Pyrococcus furiosus and Thermococcus litoralis, overview
additional information
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the isoenzyme profile in leaves changes on wounding, the change in GDH isoenzyme profile has no effect on ammonium assimilation. Protoplast isolation changes the redox state with NAD(P)H and oxidized glutathione levels increasing, and ascorbate, dehydroascorbate, NAD(P)+ and glutathione decreasing. ATP content in protoplasts declines to 2.6% of that in leaves, while that in wounded leaves increases by twofold
additional information
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the level of GDH alpha- and beta-subunits in tomato plants is regulated differently in each tomato organ
additional information
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the production of monoclonal antibodies against purified glutamate dehydrogenase from Sulfolobus solfataricus is performed with the aim to study the structure-function and evolutionary relationships between various types of glutamate dehydrogenases
additional information
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Trp243 is located in the active-site cleft. Neither Trp64 nor Trp449 are strictly required for pH-dependent inactivation
additional information
several (+/-)-2-methyl-2,4-pentanediol (MPD) binding sites with conserved sequence are identified, but AtGDH1 is insensitive to MPD in activity assays. Structure function analysis of AtGDH1, overview. The open-to-closed conformational transition is required to form a fully functional active site
additional information
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several (+/-)-2-methyl-2,4-pentanediol (MPD) binding sites with conserved sequence are identified, but AtGDH1 is insensitive to MPD in activity assays. Structure function analysis of AtGDH1, overview. The open-to-closed conformational transition is required to form a fully functional active site
additional information
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the level of GDH alpha- and beta-subunits in tomato plants is regulated differently in each tomato organ
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additional information
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the production of monoclonal antibodies against purified glutamate dehydrogenase from Sulfolobus solfataricus is performed with the aim to study the structure-function and evolutionary relationships between various types of glutamate dehydrogenases
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