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Information on EC 1.1.1.284 - S-(hydroxymethyl)glutathione dehydrogenase and Organism(s) Solanum lycopersicum and UniProt Accession D2Y3F4
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1.1.1.284 S-(hydroxymethyl)glutathione dehydrogenaseIUBMB Comments
The substrate, S-(hydroxymethyl)glutathione, forms spontaneously from glutathione and formaldehyde; its rate of formation is increased in some bacteria by the presence of EC 4.4.1.22, S-(hydroxymethyl)glutathione synthase. This enzyme forms part of the pathway that detoxifies formaldehyde, since the product is hydrolysed by EC 3.1.2.12, S-formylglutathione hydrolase. The human enzyme belongs to the family of zinc-dependent alcohol dehydrogenases. Also specifically reduces S-nitrosylglutathione.
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Word Map
- 1.1.1.284
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prodrugs
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nitroaromatic
- s-nitrosothiols
- metronidazole
- typhimurium
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nitroreduction
- flavin
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genotoxic
- beta-glucuronidase
- azoreductase
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oxygen-insensitive
- fmn
- 1-nitropyrene
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bystander
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nitrosative
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gene-directed
- nifurtimox
- beta-glucosidase
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microflora
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nitroimidazole
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gdept
- o-acetyltransferase
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tester
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nitrofuran
- 2,4,6-trinitrotoluene
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denitrosylation
- nitrofurantoin
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s-nitrosation
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nitroarenes
- nitrobenzene
- cloacae
- benznidazole
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bioreductive
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enzyme-prodrug
- nitrofurazone
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prodrug-activating
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two-electron
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single-electron
- 2-nitrofluorene
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phytoremediation
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metronidazole-resistant
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redox-based
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off-on
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explosives
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turn-on
- diagnostics
- medicine
- environmental protection
- degradation
- analysis
The taxonomic range for the selected organisms is: Solanum lycopersicum
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
nitroreductase, gsnor, s-nitrosoglutathione reductase, gsno reductase, gsnor1, adh iii, gsno-r, alcohol dehydrogenase class iii, slgsnor, formic dehydrogenase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
GSNOR
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S-nitrosoglutathione reductase
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Alcohol dehydrogenase SFA
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dehydrogenase, formaldehyde
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FALDH
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FDH
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FLD
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-
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formaldehyde dehydrogenase
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formic dehydrogenase
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-
-
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GD-FAlDH
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NAD-linked formaldehyde dehydrogenase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-(hydroxymethyl)glutathione + NAD(P)+ = S-formylglutathione + NAD(P)H + H+
structure-function analysis, active site and ligand binding structures,reaction mechanism, overview
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
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oxidation
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reduction
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PATHWAY SOURCE
PATHWAYS
BRENDA
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SYSTEMATIC NAME
IUBMB Comments
S-(hydroxymethyl)glutathione:NAD+ oxidoreductase
The substrate, S-(hydroxymethyl)glutathione, forms spontaneously from glutathione and formaldehyde; its rate of formation is increased in some bacteria by the presence of EC 4.4.1.22, S-(hydroxymethyl)glutathione synthase. This enzyme forms part of the pathway that detoxifies formaldehyde, since the product is hydrolysed by EC 3.1.2.12, S-formylglutathione hydrolase. The human enzyme belongs to the family of zinc-dependent alcohol dehydrogenases. Also specifically reduces S-nitrosylglutathione.
CAS REGISTRY NUMBER
COMMENTARY
9028-84-6
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-(hydroxymethyl)glutathione + NAD+
S-formylglutathione + NADH + H+
-
-
-
?
S-nitrosoglutathione + NADH
? + NAD+
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a variety of products depending on cellular conditions, including glutathione disulfide, glutathione sulfinamide and hydroxylamine
-
?
S-nitrosoglutathione + NADH + H+
GSSG + ammonia + NAD+
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-
-
ir
S-nitrosoglutathione + NAD(P)H + H+
GSSG + ammonia + NAD(P)+
-
-
-
ir
S-nitrosoglutathione + NADPH + H+
GSSG + ammonia + NADP+
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-
-
ir
additional information
?
-
the reaction mechanism involved the oxidation of a hydroxyl group of S-(hydroxymethyl)glutathione, spontaneous adduct of formaldehyde and glutathione, to form S-formylglutathione. Substrate specificity with alcohols and omega-hydroxyfatty acids, overview
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-
?
additional information
?
-
-
the reaction mechanism involved the oxidation of a hydroxyl group of S-(hydroxymethyl)glutathione, spontaneous adduct of formaldehyde and glutathione, to form S-formylglutathione. Substrate specificity with alcohols and omega-hydroxyfatty acids, overview
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-
?
additional information
?
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in the dehydrogenase mode, GSNOR using NAD+ as a coenzyme the oxidation of S-hydroxymethylglutathione (HMGSH), spontaneously formed from formaldehyde and glutathione to S-formylglutathione, which is further hydrolyzed to glutathione and formate by S-formylglutathione hydrolase. In the reductase mode, GSNOR catalyzes the reduction of S-nitrosoglutathione (GSNO) using NADH to an unstable intermediate N-hydroxysulfinamide (GSNHOH). Depending on the local concentration of GSH, GSNHOH is either decomposed to glutathione disulfide (GSSG) and hydroxylamine at high GSH levels, or at low GSH levels spontaneously converts to glutathione sulfinamid (GSONH2), which can be hydrolyzed to glutathione sulfinic acid (GSOOH) and ammonia. Another factor involved in the regulation of GSNO turnover is the accessibility of NADH, a co-substrate in the reduction of GSNO
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additional information
?
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plant GSNOR catalyzes the oxidation of HMGSH, geraniol, cinnamyl alcohol, omega-hydroxyfatty acids, and aliphatic alcohols with chains longer than four carbons, to corresponding aldehydes using NAD+ as a coenzyme. Short-chain alcohols, e.g. ethanol and propanol, are not enzyme substrates. In the reductase mode, plant GSNOR preferentially catalyzes the reduction of GSNO, while reactions with either aliphatic or aromatic aldehydes are insignificant. GSNO is reduced with 15-20times higher catalytic efficiency compared to the oxidation of HMGSH
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-(hydroxymethyl)glutathione + NAD+
S-formylglutathione + NADH + H+
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-
-
?
S-nitrosoglutathione + NADH
? + NAD+
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a variety of products depending on cellular conditions, including glutathione disulfide, glutathione sulfinamide and hydroxylamine
-
?
S-nitrosoglutathione + NADH + H+
GSSG + ammonia + NAD+
-
-
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ir
additional information
?
-
in the dehydrogenase mode, GSNOR using NAD+ as a coenzyme the oxidation of S-hydroxymethylglutathione (HMGSH), spontaneously formed from formaldehyde and glutathione to S-formylglutathione, which is further hydrolyzed to glutathione and formate by S-formylglutathione hydrolase. In the reductase mode, GSNOR catalyzes the reduction of S-nitrosoglutathione (GSNO) using NADH to an unstable intermediate N-hydroxysulfinamide (GSNHOH). Depending on the local concentration of GSH, GSNHOH is either decomposed to glutathione disulfide (GSSG) and hydroxylamine at high GSH levels, or at low GSH levels spontaneously converts to glutathione sulfinamid (GSONH2), which can be hydrolyzed to glutathione sulfinic acid (GSOOH) and ammonia. Another factor involved in the regulation of GSNO turnover is the accessibility of NADH, a co-substrate in the reduction of GSNO
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-
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S-nitrosoglutathione + NAD(P)H + H+
GSSG + ammonia + NAD(P)+
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-
-
ir
S-nitrosoglutathione + NADPH + H+
GSSG + ammonia + NADP+
-
-
-
ir
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
GSNOR cannot use NADPH in the reduction of GSNO
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NADH
the coenzyme binding is associated with the catalytic zinc atoms movement towards Glu70 in the catalytic domain in a hydrogen-bonding interaction with the carboxylate oxygen of Glu70. In the SlGSNOR structure crystallized with NADH and GSH, the enzyme appears in closed conformation
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
GSNOR expression is induced by Fe deficiency in tomato leaves and roots, while its overexpression alleviates chlorosis under Fe-deficiency conditions. GSNOR overexpression positively regulates the Fe distribution from root to shoot, which might result from the transcriptional regulation of genes involved in Fe metabolism
Zn2+
additional information
Zn2+
required for the oxidation reaction. The catalytic zinc ion functions as a Lewis acid, is bound by Cys177 and Cys47, His69 and either Glu70 or water (hydroxide anion). The structural zinc is bound by four cysteines, Cys99, Cys102, Cys105, and Cys113
Zn2+
each catalytic domain includes two zinc atoms. One of them is involved in the catalytic mechanism by activating the hydroxyl and carbonyl groups of substrates for transfer of hydride, and is bonded to Cys47, Cys177, His69, and either Glu70 or a water molecule. The second zinc atom is considered to have purely a structural role and is coordinated to four cysteine residues, Cys99, Cys102, Cys105, and Cys113. From the crystal structure is determined, that the catalytic zinc atoms in the apoenzyme are in a tetrahedral configuration, H-bonded to Cys47, Cys177, His69 and coordinated to the molecule of water in the active site. The coenzyme binding is associated with the catalytic zinc atoms movement towards Glu70 in the catalytic domain in a hydrogen-bonding interaction with the carboxylate oxygen of Glu70. Zinc atoms are in a tetrahedral configuration coordinated with Cys47, Cys177, His69, and Glu70, and they are no longer coordinated with the water molecule
Zn2+
required, Solanum lycopersicum SlGSNOR structure in coordination with NAD+, the active sites on the homodimer coordinate the zinc ion, a possible point of regulation in the presence of oxidative species
Zn2+
the enzyme is a homodimer coordinating two zinc atoms per subunit
additional information
other monovalent and bivalent cations, besides Hg2+ or Ag+, have only a small effect
additional information
-
other monovalent and bivalent cations, besides Hg2+ or Ag+, have only a small effect
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
inhibits both the reductase and dehydrogenase reactions by 30% at 1 mM
ascorbic acid
inhibits both the reductase and dehydrogenase reactions by 30% at 1 mM
dithiothreitol
inhibits both the reductase and dehydrogenase reactions by 30% at 1 mM
N6022
a pyrolle-based compound, that is a significantly stronger noncompetitive inhibitor compared to fatty acids, inhibiting SlGSNOR at nanomolar concentrations
S-Methylglutathione
noncompetitive inhibitor, inhibits GSNO reduction
additional information
lacking an S-nitrosyl or S-hydroxymethyl group that binds to the active site zinc atom, the affinity of inhibitors GSH and S-methylglutathione is reduced by 2-3 orders of magnitude compared to GSNO and HMGSH
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additional information
oxidative post-translationally modification of GSNOR inhibits the activity of the enzyme suggesting a direct crosstalk between reactive oxygen species (ROS)- and reactive nitrogen species (RNS)-signaling
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additional information
plant systems reversibly inhibit their GSNOR activity in response to oxidative radicals
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.057
S-nitrosoglutathione
pH and temperature not specified in the publication
0.058
S-(hydroxymethyl)glutathione
pH 8.0, 30°C, recombinant enzyme
0.058
S-(hydroxymethyl)glutathione
pH and temperature not specified in the publication
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
significantly negative regulation of GSNOR on the fifth axillary buds outgrowth
additional information
the enzyme is highly expressed in the pistil and stamens and in fruits during ripening
additional information
expression is higher in roots and stems compared to leaves of young plants
additional information
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expression is higher in roots and stems compared to leaves of young plants
additional information
GSNOR expression and activity during development of Solanum spp. genotypes. Highest expression level in stems, high expression in roots and senescent leaves, moderate expression in mature leaves and apex, low in seedlings, overview. GSNOR localizes mainly in the vascular tissue and epidermal cells of the leaf sections
additional information
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GSNOR expression and activity during development of Solanum spp. genotypes. Highest expression level in stems, high expression in roots and senescent leaves, moderate expression in mature leaves and apex, low in seedlings, overview. GSNOR localizes mainly in the vascular tissue and epidermal cells of the leaf sections
additional information
GSNOR is thought to be localized in the phloem and xylem parenchyma cells of the vasculature
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
the enzyme belongs to the large alcohol dehydrogenase superfamily, namely to the class III ADHs
evolution
GSNOR belongs to the class III alcohol dehydrogenase family
evolution
GSNOR expression and activity during development of Solanum spp. genotypes
evolution
GSNOR is evolutionarily conserved, it is reclassified as S-(hydroxymethyl)glutathione dehydrogenase (EC 1.1.1.284). FALDH and ADH3 are identical enzymes. GSNOR also is a Zn-dependent medium-chain class III alcohol dehydrogenase (ADH3, EC 1.1.1.1). GSNOR also is glutathione-dependent formaldehyde dehydrogenase (FALDH, EC 1.2.1.1). Eukaryotic GSNORs are highly conserved and unusually cysteine-rich proteins
evolution
S-nitrosoglutathione reductase (GSNOR) is highly conserved enzyme amongst eukaryotes and prokaryotes. It is a member of the class III alcohol dehydrogenase family
malfunction
depletion of GSNOR function impacts tomato (Solanum lycopersicum. L) fruit development. Thus, reduction of GSNOR expression through RNAi modulated both fruit formation and yield, establishing another function for GSNOR. Further, depletion of Solanum lycopersicum GSNOR (SlGSNOR) additionally impacted a number of other developmental processes, including seed development, which also has not been previously linked with GSNOR activity. Depletion of GSNOR function does not influence root development in tomato. Reduction of GSNOR transcript abundance compromises plant immunity. Overexpression of SlGSNOR promotes resistance to bacterial pathogens, such as Pseudomonas syringae pv. tomato DC3000 (PstDC3000)
malfunction
GSNOR knockout mutated plants often display a stunted growth phenotype in all structures, and exhibit a pre-induced protective effect against oxidative stressors, as well as an improved immune response associated with NO accumulation in roots. The action of increasing NO levels and GSNOR1 inhibition is often coupled with increased ROSs associated with plant immune response. Plant systems reversibly inhibit their GSNOR activity in response to oxidative radicals
malfunction
GSNOR overexpression in tomato plant has little effect on growth and development, whereas GSNOR downregulated plants are significantly smaller, suggesting a role for NO and S-nitrosothiol signaling
malfunction
identification of 334 endogenously S-nitrosylated proteins with 425 S-nitrosylated sites site-specific nitrosoproteomic approach from the wild-type and GSNOR-knockdown tomato plants under both control and sodic alkaline stress conditions, detailed overview. These S-nitrosylated proteins are involved in a wide range of various metabolic, cellular and catalytic processes
malfunction
overexpression alleviates chlorosis under Fe-deficiency conditions. GSNOR overexpression positively regulates the Fe distribution from root to shoot, which might result from the transcriptional regulation of genes involved in Fe metabolism. Overexpression of GSNOR maintains redox homeostasis and protects chloroplasts from Fe deficiency-related damage, resulting in a greater photosynthetic capacity. As a nitric oxide regulator, GSNOR's overexpression decreases the excessive accumulation of nitric oxide and S-nitrosothiols during the Fe deficiency, and maintains the homeostases of reactive oxygen species and reactive nitrogen species. Moreover, GSNOR overexpression, probably at the level of genes and proteins, along with protein S-nitrosylation, promotes Fe uptake and regulates the shoot/root Fe ratio under Fe-deficiency conditions. The overexpression of GSNOR alleviates the Fe-deficiency-induced oxidative stress
malfunction
oxidative post-translationally modification of GSNOR inhibits the activity of the enzyme suggesting a direct crosstalk between ROS- and RNS-signaling, regulatory effects of reactive oxygen species (ROS) on GSNOR, overview. In tomato, the expression of GSNOR is significantly affected by alkaline stress. Physiological function of ROS-dependent inhibition of GSNOR
malfunction
suppression of S-nitrosoglutathione reductase (GSNOR) promotes axillary buds outgrowth via inhibiting the expression of flavin monooxygenase (FZY) in both apical and axillary buds. Meanwhile, AUX1 and PIN1 are downregulated in apical buds but upregulated in axillary buds in GSNOR-suppressed plants. Thus, reduced indoleacetic acid (IAA) accumulation is shown in both apical buds and axillary buds of GSNOR-suppressed plants. A decreased ratio of auxin:cytokinin is observed in axillary buds of GSNOR-suppressed plants, leading to buds dormancy breaking. GSNOR plays a positive role in regulating FZY expression and IAA level in apical buds. Notably, levels of IAA in axillary buds show similar patterns with that in apical buds, but an inhibition of FZY transcript in axillary buds is observed by both overexpression and suppression of GSNOR. Silencing FZY results in auxin biosynthesis inhibition and axillary buds outgrowth. Inhibitory effects on FZY expression and IAA accumulation lead to highly branched phenotype in tomato plants
metabolism
along with its more stable NO donor, S-nitroso-glutathione (GSNO), formed by NO non-enzymatically in the presence of glutathione (GSH), NO is a redox-active molecule capable of mediating target protein cysteine thiols through the post translational modification, S-nitrosation. S-nitroso-glutathione reductase (GSNOR) thereby acts as a mediator to pathways regulated by NO due to its activity in the irreversible reduction of GSNO to oxidized glutathione (GSSG) and ammonia. GSNOR is thought to be pleiotropic and often acts by mediating the cellular environment in response to stress conditions. Under optimal conditions its activity leads to growth by transcriptional upregulation of the nitrate transporter, NRT2.1, and through its interaction with phytohormones like auxin and strigolactones associated with root development. GSNOR is required in times of iron toxicity. Mechanism for control of the nitrogen assimilation pathway. GSNOR activity is thought to increase NRT2.1 and nitrate reductase (NR) function thereby leading to eventual increases in NO levels, which are ultimately thought to have an inhibitory effect on GSNOR
metabolism
role of S-nitrosoglutathione reductase in the regulation of reactive nitrogen species metabolism in Solanum spp., modeling, overview
metabolism
site-specific nitrosoproteomic analysis, GSNOR is the key scavenger for sodic alkaline stress-induced S-nitrosylation
physiological function
in plants, GSNOR plays an important role in biotic and abiotic stress responses. S-nitrosylglutathione serves as a nitric oxide reservoir locally or possibly as NO donor in distant cells and tissues. NO and NO-related molecules such as S-nitrosothiols play a central role in the regulation of normal plant physiological processes and host defence. The key enzyme participates in the cellular homeostasis of S-NOs and in the metabolism of reactive nitrogen species
physiological function
enzyme GSNOR is a nitric oxide regulator and is involved in responses to iron deficiency, GSNOR-regulated RNS homeostasis under Fe-deficiency conditions, overview. Ferric-chelate reductase activity is regulated by GSNOR
physiological function
key role of GSNOR and modulations of reactive nitrogen species (RNS) during plant development under normal conditions pointing to their involvement in molecular mechanisms of tomato responses to biotrophic pathogens on local and systemic levels
physiological function
nitric oxide (NO) is emerging as a key signalling molecule in plants. The chief mechanism for the transfer of NO bioactivity is thought to be S-nitrosylation, the addition of an NO moiety to a protein cysteine thiol to form an S-nitrosothiol (SNO). The enzyme S-nitrosoglutathione reductase (GSNOR) indirectly controls the total levels of cellular S-nitrosylation, by depleting S-nitrosoglutathione (GSNO), the major cellular NO donor. SlGSNOR regulates seed devlopment, fruit production, and flower development, overview
physiological function
nitric oxide radical (radical NO) acts as signaling molecule in plants being involved in diverse physiological processes such as germination, root growth, stomata closing and response to biotic and abiotic stress. S-Nitrosoglutathione (GSNO) is the storage and transport form of radical NO and has a very important function in radical NO signaling since it can transfer its radical NO moiety to other proteins (trans-nitrosylation). The level of GSNO and thus the level of S-nitrosylated proteins are regulated by GSNO-reductase (GSNOR). In this way, this enzyme regulates the S-nitrosothiol levels and plays a balancing role in fine-tuning radical NO signaling
physiological function
S-nitrosoglutathione reductase (GSNOR) is capable of the NADH-dependent reduction of GSNO to glutathione disulfide (GSSG), the oxidized form of GSH, and ammonium (NH3). It has been originally identified in plants as a glutathione-dependent formaldehyde dehydrogenase (FALDH), and a member of the class III alcohol dehydrogenase family, where the primary substrate is hemithioacetal S-hydroxymethylglutathione (HMGSH), which is formed in an oxidizing environment through the favorable reaction of formaldehyde and GSH, using a catalytic zinc, and in the presence of the coenzyme NAD+. The redox-active enzyme acts in the homeostasis of S-nitrosothiols (SNOs) and is capable of regulating many cellular processes in that manner. Role of GSNOR in root development, overview. Although it is expressed within many plant tissues, GSNOR is thought to be localized in the phloem and xylem parenchyma cells of the vasculature, capable of regulating NO levels throughout the plant. GSNOR activity is related to NO production. Auxin is an important hormone capable of mediating cellular growth in concert with GSNOR. Auxin signalling is specifically relevant when considering the growth of root structures in response to GSNO levels, where a mechanism has been identified to regulate TIR1, a nuclear F-box protein and the auxin receptor. At increased GSNO levels, and thereby reduced GSNOR activity, S-nitrosation of TIR1 receptor is thought to increase its ax0enity for auxin and in turn increase transcription of target proteins. GSNOR may play a role in controlling strigolactones (SL) induced primary root elongation
physiological function
S-nitrosoglutathione reductase (GSNOR) is the master regulator of protein S-nitrosation in plant NO signaling. GSNOR functions are mediated by its enzymatic activity, which catalyzes irreversible GSNO conversion to oxidized glutathione within the cellular catabolism of nitric oxide. GSNOR is involved in the maintenance of balanced levels of reactive nitrogen species and in the control of cellular redox state. Multiple functions of GSNOR in plant development via NO-dependent and -independent signaling mechanisms and in plant defense responses to abiotic and biotic stress conditions. It is the key enzyme of the regulation of S-nitrosation and formaldehyde detoxification. Via removing GSNO, GSNOR plays a critical role in the metabolism of RNSs, in the homeostasis of intracellular levels of NO and in control of the trans-nitrosation equilibrium between S-nitrosylated proteins and GSNO, the most common low-molecular weight S-nitrosothiol. In trans-nitrosation reactions, the nitroso group is transferred among thiols on proteins and low-molecular weight peptides. GSNO reduction by GSNOR is an irreversible reaction, and the products can no longer nitrosate cellular proteins. GSNOR is a cytosolic enzyme that catalyzes the NADH-dependent reduction of GSNO, leading to the formation of glutathione disulfide (GSSG) and ammonium. GSNOR also is glutathione-dependent formaldehyde dehydrogenase (FALDH, EC 1.2.1.1). The proper substrate for FALDH is the hemithioacetal S-hydroxymethylglutathione (HMGSH), formed nonenzymatically from formaldehyde and glutathione. The enzyme is reclassified as S-(hydroxymethyl)glutathione dehydrogenase. Enzyme reactions overview. Since GSNOR cannot use NADPH in the reduction of GSNO, it is controlled by NADH availability and increasing levels of NADH are proposed to trigger the GSNO reduction. GSNOR enzymes themselves produce NADH in the process of the oxidation of formaldehyde, formaldehyde likely triggers the reduction of GSNO, regulation of the enzyme, overview. GSNOR is involved in plant responses to cold and heat stress
physiological function
S-nitrosoglutathione reductase (GSNOR) negatively regulates NO homeostasis. GSNOR-mediated changes of NO and auxin affect cytokinin biosynthesis, transport, and signaling. suppression of GSNOR decreased the transcripts of AUX1 and PIN1 in apical buds, but increased the transcripts of AUX1 and PIN1 in axillary buds. GSNOR-controlled NO plays important roles in controlling axillary buds outgrowth via altering the homeostasis and signaling of auxin and cytokinin in tomato plants
physiological function
S-nitrosylation, regulated by S-nitrosoglutathione reductase (GSNOR), is considered as an important route for nitric oxide (NO)-modulated stress tolerance in plants. Proteins involving in NO homeostasis control, signaling of Ca2+, ethylene and MAPK, reactive oxygen species (ROS) scavenging, osmotic regulation, as well as energy support pathway are identified and selected as the key and sensitive targets that are regulated by GSNOR-modulated S-nitrosylation in response to sodic alkaline stress. GSNOR is actively involved in the regulation of sodic alkaline stress tolerance by S-nitrosylation. Phenotypes, overview
additional information
cysteine residues are targets for reversible and irreversible redox-modifications and play an important role in redox signaling. GSNOR is remarkably cysteine rich. In total plant GSNORs have 14 to 16 cysteine residues. Thirteen of them are highly conserved within plant GSNORs. Three of them (Cys10, Cys271, Cys370) are located on the protein surface making them directly accessible for post-translational modifications. Moreover, three cysteine residues (Cys47, Cys177, Cys271) are located in the substrate binding site, where Cys47 and Cys177 are coordinating the catalytic Zn2+ together with His69 and a water molecule. The structural Zn2+ is coordinated by Cys99, Cys102, Cys105, and Cys113. Accessibility and physico-chemical features of cysteine residues define their redox-reactivity and the 3-dimensional structure of GSNOR allows to identifying such surface-exposed, redox-sensitive cysteine residues
additional information
Solanum lycopersicum SlGSNOR structure in coordination with NAD+, the active sites on the homodimer coordinate the zinc ion, a possible point of regulation in the presence of oxidative species
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). D2Y3F4_SOLLC
379
0
40674
TrEMBL
other Location (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homodimer
additional information
tomato GSNOR is a homodimeric enzyme consisting of two 40 kDa subunits containing a big catalytic and a small coenzyme-binding domain with an active site localized in a cleft between them. Non-catalytic domain includes a binding site for NAD+ coenzyme: six beta-strands of each coenzyme-binding domain form 12 pseudo-continuous beta-sheets. Each catalytic domain includes two zinc atoms. One of them is involved in the catalytic mechanism by activating the hydroxyl and carbonyl groups of substrates for transfer of hydride, and is bonded to Cys47, Cys177, His69, and either Glu70 or a water molecule. The second zinc atom is considered to have purely a structural role and is coordinated to four cysteine residues, Cys99, Cys102, Cys105, and Cys113
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structures of SlGSNOR apoenzyme, binary complex with NAD+ and a structure crystallized in the presence of NADH and GSH. Catalytic domains of the apoenzyme and of the binary complex with NAD+ are both in the semi-open conformation. The catalytic zinc atoms in the apoenzyme are in a tetrahedral configuration, H-bonded to Cys47, Cys177, His69 and coordinated to the molecule of water in the active site. The coenzyme binding is associated with the catalytic zinc atoms movement towards Glu70 in the catalytic domain in a hydrogen-bonding interaction with the carboxylate oxygen of Glu70. Zinc atoms are in a tetrahedral configuration coordinated with Cys47, Cys177, His69, and Glu70, and they are no longer coordinated with the water molecule. In the SlGSNOR structure crystallized with NADH and GSH, the enzyme appears in closed conformation. Structue analysis, overview
purified recombinant His-tagged enzyme, in complex with NAD+ and with NADH, hanging drop vapour diffusion, mixing of 0.003 ml of 22 mg/ml protein in 20 mM Tris-HCl, pH 8.0, 100 mM NaCl, 2.5 mM NAD+, or 2.5 mM NADH and 5.0 mM GSH, 20°C, X-ray diffraction tructure determination and analysis at 1.85-2.14 A resolution, molecular replacement and modeling
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
construction of GSNOR knockout plants that exhibit overall reductions in growth where root development, thought to be directly linked to redox activity. The GSNOR knockout mutant contains a pre-induced antioxidant protection system
additional information
enzyme SlGSNOR knockout by gene silencing with RNAi using Agrobacterium tumefaciens transfection method. The accumulation of SlGSNOR1 transcripts is tightly regulated in tomato MicroTom and a significant reduction in its expression leads to lethality, as SlGSNOR-RNAi lines with greater than about 60% reduction in SlGSNOR1 expression are not viable. Both SlGSNOR-RNAi and SlGSNOR-overexpressing(OE) lines convey significant effects on the overall development of tomato plants, ranging from seed germination to fruiting and net yield per plant. Reduced GSNOR expression in SlGSNOR-RNAi lines drastically affects seed development and reduces the number of seeds produced in the fruits of the resulting transgenic plants, phenotype, overview. SlGSNOR-RNAi plants also show faster germination as compared with wild-type and SlGSNOR-OE plants on either MS medium or soil, and show the appearance of fresh green tissues at least 1 d before the wild-type and overexpressing plants
additional information
-
enzyme SlGSNOR knockout by gene silencing with RNAi using Agrobacterium tumefaciens transfection method. The accumulation of SlGSNOR1 transcripts is tightly regulated in tomato MicroTom and a significant reduction in its expression leads to lethality, as SlGSNOR-RNAi lines with greater than about 60% reduction in SlGSNOR1 expression are not viable. Both SlGSNOR-RNAi and SlGSNOR-overexpressing(OE) lines convey significant effects on the overall development of tomato plants, ranging from seed germination to fruiting and net yield per plant. Reduced GSNOR expression in SlGSNOR-RNAi lines drastically affects seed development and reduces the number of seeds produced in the fruits of the resulting transgenic plants, phenotype, overview. SlGSNOR-RNAi plants also show faster germination as compared with wild-type and SlGSNOR-OE plants on either MS medium or soil, and show the appearance of fresh green tissues at least 1 d before the wild-type and overexpressing plants
additional information
GSNOR knockdown tomato lines are established by RNA interference (RNAi) approach
additional information
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GSNOR knockdown tomato lines are established by RNA interference (RNAi) approach
additional information
there are no significant changes in the physiological or chlorophyll fluorescence parameters between tomato leaves of wild-type and transgenic GSNOR overexpressing lines under control conditions. In contrast, apparent chlorosis is observed in the wild-type lines after 20 d under Fe-deficiency conditions, while transgenic lines show significantly higher Fe-deficiency tolerance levels than wild-type lines as assessed by morphological characteristics, especially the color of the stem apices and new leaves
additional information
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there are no significant changes in the physiological or chlorophyll fluorescence parameters between tomato leaves of wild-type and transgenic GSNOR overexpressing lines under control conditions. In contrast, apparent chlorosis is observed in the wild-type lines after 20 d under Fe-deficiency conditions, while transgenic lines show significantly higher Fe-deficiency tolerance levels than wild-type lines as assessed by morphological characteristics, especially the color of the stem apices and new leaves
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant N-terminally His-tagged enzyme from Escherichia coli by methal chelating chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene ADH3, recombinant expression of GFP-tagged enzyme in Solanum lycopersicum leaves, mainly in the vascular tissue and epidermal cells
gene ADH3, recombinant overexpression of enzyme GSNOR in Solanum lycopersicum using Agrobacterium-mediated transformation of the CaMV35S::GSNOR overexpression construct, quantitative real-time PCR enzyme expression analysis
real-time PCR expression analysis, recombinant expression in Escherichia coli as N-terminally His-tagged enzyme
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme GSNOR is downregulated in plants infected with Pseudoidium neolycopersici, the causative agent of tomato powdery mildew. Solanum lycopersicum is highly susceptible against Pseudoidium neolycopersici infection. The susceptible genotype Solanum lycopersicum cv. Amateur shows higher GSNOR activity compared to two other genotypes, except for leaves
GSNOR is thought to be upregulated under iron deficient conditions. Fe-deficiency leads to NO, GSNO, and GSH decrease leading to changes in growth probably regulated by GSNOR localized in the phloem
in tomato, the expression of GSNOR is significantly affected by alkaline stress. In particular, transcription of GSNOR is inhibited dramatically in response to alkaline stress between 0.5 and 2 d after treatment. Afterwards, the expression of GSNOR starts to increase at 3 d after NaHCO3 treatment, peaks on the sixth day, and then declines
response to highly nitrosative and oxidative conditions its activity is often downregulated, possibly through an S-nitrosation site on GSNOR at Cys271
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kubienova, L.; Kopecny, D.; Tylichova, M.; Briozzo, P.; Skopalova, J.; Sebela, M.; Navratil, M.; Tache, R.; Luhova, L.; Barroso, J.B.; Petrivalsky, M.
Structural and functional characterization of a plant S-nitrosoglutathione reductase from Solanum lycopersicum
Biochimie
95
889-902
2013
Solanum lycopersicum (D2Y3F4), Solanum lycopersicum, Solanum lycopersicum Amateur (D2Y3F4)
Ventimiglia, L.; Mutus, B.
The physiological implications of S-nitrosoglutathione reductase (GSNOR) activity mediating NO signalling in plant root structures
Antioxidants (Basel)
9
1206
2020
Solanum lycopersicum (D2Y3F4), Arabidopsis thaliana (F4K7D6)
Lindermayr, C.
Crosstalk between reactive oxygen species and nitric oxide in plants key role of S-nitrosoglutathione reductase
Free Radic. Biol. Med.
122
110-115
2018
Camelina sativa, Medicago truncatula (A0A072VKC1), Noccaea caerulescens (A0A1J3JHF1), Nicotiana sylvestris (A0A1U7Y0I8), Helianthus annuus (A0A251UXN7), Populus trichocarpa (A0A2K2BPI4), Oryza sativa Indica Group (A2XAZ3), Chlamydomonas reinhardtii (A8IY20), Zea mays (B6T6Q8), Ricinus communis (B9T5W1), Brassica juncea (C4PKK5), Solanum lycopersicum (D2Y3F4), Volvox carteri f. nagariensis (D8U4T8), Arabidopsis thaliana (F4K7D6), Lactuca sativa (J7GHV7), Pisum sativum (P80572), Capsella rubella (R0EWH3)
Hussain, A.; Yun, B.W.; Kim, J.H.; Gupta, K.J.; Hyung, N.I.; Loake, G.J.
Novel and conserved functions of S-nitrosoglutathione reductase in tomato
J. Exp. Bot.
70
4877-4886
2019
Solanum lycopersicum (D2Y3F4), Solanum lycopersicum
Wen, D.; Sun, S.; Yang, W.; Zhang, L.; Liu, S.; Gong, B.; Shi, Q.
Overexpression of S-nitrosoglutathione reductase alleviated iron-deficiency stress by regulating iron distribution and redox homeostasis
J. Plant Physiol.
237
1-11
2019
Solanum lycopersicum (D2Y3F4), Solanum lycopersicum
Yan, Y.; Shi, Q.; Gong, B.
S-nitrosoglutathione reductase-mediated nitric oxide affects axillary buds outgrowth of Solanum lycopersicum L. by regulating auxin and cytokinin signaling
Plant Cell Physiol.
62
458-471
2021
Solanum lycopersicum (D2Y3F4), Solanum lycopersicum
Gong, B.; Shi, Q.
Identifying S-nitrosylated proteins and unraveling S-nitrosoglutathione reductase-modulated sodic alkaline stress tolerance in Solanum lycopersicum L.
Plant Physiol. Biochem.
142
84-93
2019
Solanum lycopersicum (D2Y3F4), Solanum lycopersicum
Jahnova, J.; Cincalova, L.; Sedlarova, M.; Jedelska, T.; Sekaninova, J.; Mieslerova, B.; Luhova, L.; Barroso, J.B.; Petrivalsky, M.
Differential modulation of S-nitrosoglutathione reductase and reactive nitrogen species in wild and cultivated tomato genotypes during development and powdery mildew infection
Plant Physiol. Biochem.
155
297-310
2020
Solanum lycopersicum (D2Y3F4), Solanum lycopersicum, Solanum habrochaites (E9ND18), Solanum habrochaites, Solanum chmielewskii (E9ND19)
Jahnova, J.; Luhova, L.; Petrivalsky, M.
S-nitrosoglutathione reductase - the master regulator of protein S-nitrosation in plant NO signaling
Plants (Basel)
8
48
2019
Oryza sativa, Cucumis sativus (A0A0A0KBZ1), Cucumis melo (A0A1S3CB00), Nicotiana tabacum (A0A1S3ZYT7), Helianthus annuus (A0A251UXN7), Physcomitrium patens (A0A2K1JM97), Chlamydomonas reinhardtii (A0A2K3D6Q9), Nicotiana attenuata (A0A314KZZ1), Solanum lycopersicum (D2Y3F4), Lotus japonicus (I3ST14), Pisum sativum (P80572), Solanum tuberosum (Q2XPW7), Arabidopsis thaliana (Q96533)
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