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Information on EC 1.8.1.7 - glutathione-disulfide reductase and Organism(s) Saccharomyces cerevisiae and UniProt Accession P41921

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IUBMB Comments
A dimeric flavoprotein (FAD); activity is dependent on a redox-active disulfide in each of the active centres.
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This record set is specific for:
Saccharomyces cerevisiae
UNIPROT: P41921
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The taxonomic range for the selected organisms is: Saccharomyces cerevisiae
The enzyme appears in selected viruses and cellular organisms
Synonyms
glutathione reductase, gsh reductase, gssg reductase, glutathione disulfide reductase, ptgr2, gsr-1, glutathione-disulfide reductase, glutathione s-reductase, thioredoxin/glutathione reductase, nadph-glutathione reductase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glutathione reductase
-
glutathione reductase Glr1
-
EC 1.6.4.2
-
formerly
glutathione reductase
glutathione reductase (NADPH)
-
-
-
-
glutathione S-reductase
-
-
-
-
GOR1
-
-
-
-
GOR2
-
-
-
-
GRase
-
-
-
-
GSH reductase
-
-
-
-
GSSG reductase
-
-
-
-
NADPH-glutathione reductase
-
-
-
-
NADPH-GSSG reductase
-
-
-
-
NADPH:oxidized-glutathione oxidoreductase
-
-
-
-
OBP29
-
-
-
-
reductase, glutathione
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
2 glutathione + NADP+ = glutathione disulfide + NADPH + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
glutathione:NADP+ oxidoreductase
A dimeric flavoprotein (FAD); activity is dependent on a redox-active disulfide in each of the active centres.
CAS REGISTRY NUMBER
COMMENTARY hide
9001-48-3
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
glutathione disulfide + NADPH + H+
2 glutathione + NADP+
show the reaction diagram
-
-
-
?
GSSG + NADPH + H+
glutathione + NADP+
show the reaction diagram
-
-
-
?
bis-N,N'-(gamma-glutamylcystine) + NADPH + H+
?
show the reaction diagram
-
-
-
-
r
bis-N-chloro-gamma-L-glutamyl derivative of GSSG + NADPH + H+
? + glutathione + NADP+
show the reaction diagram
-
-
-
-
?
glutathione disulfide + NADPH
glutathione + NADP+
show the reaction diagram
-
-
-
-
?
glutathione disulfide + NADPH + H+
2 glutathione + NADP+
show the reaction diagram
-
-
-
-
?
glutathione disulfide + NADPH + H+
glutathione + NADP+
show the reaction diagram
glutathione-S-sulfonate + NADPH + H+
?
show the reaction diagram
-
-
-
-
r
GSSG + NADPH
glutathione + NADP+
show the reaction diagram
GSSG + NADPH + H+
glutathione + NADP+
show the reaction diagram
-
-
-
-
?
S-allylmercaptoglutathione disulfide + NADPH + H+
2 S-allylmercaptoglutathione + NADP+
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
glutathione disulfide + NADPH + H+
2 glutathione + NADP+
show the reaction diagram
-
-
-
?
glutathione disulfide + NADPH
glutathione + NADP+
show the reaction diagram
-
-
-
-
?
glutathione disulfide + NADPH + H+
2 glutathione + NADP+
show the reaction diagram
-
-
-
-
?
glutathione disulfide + NADPH + H+
glutathione + NADP+
show the reaction diagram
-
-
-
-
ir
GSSG + NADPH
glutathione + NADP+
show the reaction diagram
S-allylmercaptoglutathione disulfide + NADPH + H+
2 S-allylmercaptoglutathione + NADP+
show the reaction diagram
-
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
flavin
-
flavoprotein
NADPH
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zn2+
-
glutathione reductase is non-competitively inhibited up to 2 mM and activated above this concentration
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
hypericin
when is glutathione disulfide is the variable substrate, hypericin inhibits the enzyme competitively
1,3-Bis-(2-chloroethyl)-1-nitrosourea
-
-
1-Fluoro-2,4-dinitrobenzene
-
reversible
2-Chloroethylisocyanate
-
-
acetaminophen-glutathione conjugate
-
the enzyme activity is inhibited to 52.7% after treatment with 2.96 mM acetaminophen-glutathione conjugate, at pH 7.6 at 25°C
acylfulvene
-
reversible inhibition, less than 10% residual activity at 1.25 mM, inhibition by 1.0 or 1.25 mM acylfulvene is reduced by 30% in the presence of NDPH
Ca2+
-
inhibition is non-competitive with respect to GSSG and uncompetitive with respect to NADPH
carmustine
-
i.e. 1,3-bis(2-chloroethyl)-1-nitroso-urea, irreversible inhibitor, complete inhibition at 0.625 mM
cisplatin
-
0.01-0.2 mM
Cu+
-
presence of Cu+ inhibits noncompetitively with respect to the substrate GSSG and NADPH and inactivates with the cleavage of a peptide bond of the enzyme. Inactivation/fragmentation is prevented by addition of catalase
Fe2+
-
addition of exogenous Fe2+ (but not Fe3+) potentiates NADPH-induced inactivation of glutathione reductase, after a 2 min incubation period, 0.05 mM Fe2+ plus 0.3 mM NADPH induce 57% loss of enzyme activity
H2O2
-
inactivates with the cleavage of a peptide bond of the enzyme. Inactivation/fragmentation is prevented by addition of catalase
Haemin
-
mediates covalent cross-linking and degradation of the enzyme
hydroxymethylacylfulvene
-
irreversible inhibition, less than 10% residual activity at 1.25 mM, inhibition by 0.625 or 1.25 mM hydroxymethylacylfulvene is reduced by 45% in the presence of NDPH
iodoacetamide
-
-
iodoacetate
-
in presence but not in absence of reduced coenzyme
L-gamma-glutamyl-2-methyl-L-cysteinyl-glycine disulfide
-
competitive inhibitor
monohydrated complex of cisplatin
-
0.01-0.2 mM
N-Alkylmaleimide
-
-
N-ethylmaleimide
-
-
NADPH
-
58% inhibition at 0.3 mM after 60 min incubation, exogenously added antioxidants including ethanol, dimethylsulfoxide and 2-deoxyribose do not protect glutathione reductase against NADPH-induced inactivation, whilst addition of exogenous Fe2+ (but not Fe3+) potentiates the inactivation, removal of oxygen from the medium leads to increased inhibition of glutathione reductase, whereas pre-incubation of the Fe2+-containing medium for 30 min under normoxic conditions prior to the addition of GR abolishes the enzyme inactivation by NADPH
Ni2+
-
inhibition is competitive with respect to GSSG and uncompetitive with respect to NADPH
Nitrofurantoin
-
-
oxaliplatin
-
0.01-0.2 mM
p-chloromercuriphenyl sulfonate
-
-
phenyl mercuric acetate
-
-
Phenylarsonous acid
-
-
Phenylglyoxal
-
-
pyridoxal 5'-phosphate
-
70% inactivation, due to specific modification of an epsilon-amino group lysine residue
sulfhydryl reagents
-
in presence but not in absence of reduced coenzyme
Zn2+
-
glutathione reductase is non-competitively inhibited up to 2 mM and activated above this concentration
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0746 - 0.2625
GSSG
0.015 - 0.0323
NADPH
11.6
bis-N,N'-(gamma-glutamylcystine)
-
-
0.07
glutathione disulfide
-
pH 7.5, 22°C
0.25
glutathione-S-sulfonate
-
-
0.5
S-allylmercaptoglutathione disulfide
-
pH 7.5, 22°C
-
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
463.3 - 900
NADPH
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00292
hypericin
pH 7.5, 37°C
0.00035
Cu+
-
pH 7.8, 37°C
0.001
Cu2+
0.18
hydroxymethylacylfulvene
-
at 25°C, pH not specified in the publication
0.01464
L-gamma-glutamyl-2-methyl-L-cysteinyl-glycine disulfide
-
in 100mM in potassium phosphate, pH 7.5, temperature not specified in the publication
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0185
hypericin
Saccharomyces cerevisiae
pH 7.5, 37°C
0.871
acylfulvene
Saccharomyces cerevisiae
-
at 25°C, pH not specified in the publication
0.071
carmustine
Saccharomyces cerevisiae
-
at 25°C, pH not specified in the publication
0.216
hydroxymethylacylfulvene
Saccharomyces cerevisiae
-
at 25°C, pH not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
140
-
purified enzyme
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
-
NADPH + GSSG
7.8 - 8.6
-
broad optimum
8
-
glutathione disulfide oxidation
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.6 - 10.8
-
at saturating NADPH levels
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
-
gene GLR1 uses alternative start codons to generate two forms of enzyme. Translation from the first AUG codon generates the mitochondrial form incorporating a presequence necessary for import, while translation from the second AUG codon yields the cytosolic counterpart. The N-terminus of cytosolic GLR1 normally is N-acetylserine. In a GLR1-overproducing strain, unprocessed mitochondrial GLR1 with N-terminal acetylmethionine also accumulates in the cytosol. The processed mitochondrial GLR1 has three alternative N-termini, none of them acetylated. Mitochondrial GLR1 is turned over faster than the cytosolic form by a factor of about 2. The second AUG appears to be responsible for most of the cellular GLR1
physiological function
-
the GSH pool within the cell is restored by the reduction of glutathione disulfide to glutathione by the NADPH-dependent enzyme glutathione reductase
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
118000
-
equilibrium sedimentation
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop method, crystal structure is determined at 2.40 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3
-
stable
394709
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
concentrated solution, stable for years
-
crystals and amorphous protein obtained by precipitation with ammonium sulfate are stable
-
NADP+ stabilizes
-
repeated freezing and thawing, inactivation
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, pH 6.8, 0.05 M potassium phosphate buffer, indefinitely stable
-
4°C, activation after storage over days, months or years
-
concentrated solution, years
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
overexpression of Saccharomyces cerevisiae Glr1 in Pichia pastoris GS115
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
gene GLR1 uses alternative start codons to generate two forms of enzyme. Translation from the first AUG codon generates the mitochondrial form incorporating a presequence necessary for import, while translation from the second AUG codon yields the cytosolic counterpart. The N-terminus of cytosolic GLR1 normally is N-acetylserine. In a GLR1-overproducing strain, unprocessed mitochondrial GLR1 with N-terminal acetylmethionine also accumulates in the cytosol. The processed mitochondrial GLR1 has three alternative N-termini, none of them acetylated. Mitochondrial GLR1 is turned over faster than the cytosolic form by a factor of about 2. The second AUG appears to be responsible for most of the cellular GLR1
-
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
refolding after treatment with 6 M urea, recovering of full activity
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Williams, C.H.
Flavin-containing dehydrogenases
The Enzymes, 3rd Ed. (Boyer, P. D. , ed. )
13
89-173
1976
Saccharomyces cerevisiae, Escherichia coli, Hemicentrotus pulcherrimus, Homo sapiens, Penicillium chrysogenum, Rattus norvegicus
-
Manually annotated by BRENDA team
Schirmer, R.H.; Krauth-Siegel, R.L.; Schulz, G.E.
Glutathione reductase
Coenzymes and cofactors, Glutathione, Chem. Biochem. Med. Aspects Pt. A (Dolphin D, Poulson R, Avromonic O, eds. ) John Wiley & Sons, New York
3
553-596
1989
Allochromatium vinosum, Bos taurus, Saccharomyces cerevisiae, Bufo bufo, Oryctolagus cuniculus, Escherichia coli, Meriones unguiculatus, Homo sapiens, Litomosoides carinii, Scombridae, Mus musculus, Penicillium chrysogenum, Plasmodium vinckei, Rattus norvegicus, Spinacia oleracea, Sus scrofa
-
Manually annotated by BRENDA team
Colman, R.F.
Glutathione reductase (yeast)
Methods Enzymol.
17
500-503
1971
Saccharomyces cerevisiae
-
Manually annotated by BRENDA team
Wong, K.K.; Vanoni, M.A.; Blanchard, J.S.
Glutathione reductase: solvent equilibrium and kinetic isotope effects
Biochemistry
27
7091-7096
1988
Saccharomyces cerevisiae, Homo sapiens, Spinacia oleracea
Manually annotated by BRENDA team
Harding, J.J.
Affinity chromatography in the purification of glutathione reductase
J. Chromatogr.
77
191-199
1973
Saccharomyces cerevisiae, Ovis aries, Homo sapiens, Triticum aestivum
Manually annotated by BRENDA team
Carlberg, I.; Mannervik, B.
Purification by affinity chromatography of yeast glutathione reductase, the enzyme responsible for the NADPH-dependent reduction of the mixed disulfide of coenzyme A and glutathione
Biochim. Biophys. Acta
484
268-274
1977
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Levron, B.; Burgot, G.; Burgot, J.L.
On the reduction of dithiolethiones and dithiolylium ions by NADPH and glutathione reductase
Arch. Biochem. Biophys.
382
189-194
2000
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Pandey, A.; Iyengar, L.; Katiyar, S.S.
Modification of an essential amino group of glutathione reductase from yeast by pyridoxal 5'-phosphate
J. Enzyme Inhib.
12
143-154
1997
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Landino, L.M.; Moynihan, K.L.; Todd, J.V.; Kennett, K.L.
Modulation of the redox state of tubulin by the glutathione/glutaredoxin reductase system
Biochem. Biophys. Res. Commun.
314
555-560
2004
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Witte, A.B.; Anestal, K.; Jerremalm, E.; Ehrsson, H.; Arner, E.S.
Inhibition of thioredoxin reductase but not of glutathione reductase by the major classes of alkylating and platinum-containing anticancer compounds
Free Radic. Biol. Med.
39
696-703
2005
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Nagy, P.; Ashby, M.T.
Kinetics and mechanism of the oxidation of the glutathione dimer by hypochlorous Acid and catalytic reduction of the chloroamine product by glutathione reductase
Chem. Res. Toxicol.
20
79-87
2007
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Tandogan, B.; Ulusu, N.N.
The inhibition kinetics of yeast glutathione reductase by some metal ions
J. Enzyme Inhib. Med. Chem.
22
489-495
2007
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Yu, J.; Zhou, C.
Crystal structure of glutathione reductase Glr1 from the yeast Saccharomyces cerevisiae
Proteins Struct. Funct. Bioinform.
68
972-979
2007
Saccharomyces cerevisiae (P41921), Saccharomyces cerevisiae
Manually annotated by BRENDA team
Cardoso, L.; Ferreira, S.; Hermes-Lima, M.
Reductive inactivation of yeast glutathione reductase by Fe(II) and NADPH
Comp. Biochem. Physiol. A
151
313-321
2008
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Rousar, T.; Parik, P.; Kucera, O.; Bartos, M.; Cervinkova, Z.
Glutathione reductase is inhibited by acetaminophen-glutathione conjugate in vitro
Physiol. Res.
59
225-232
2010
Saccharomyces cerevisiae, Rattus norvegicus
Manually annotated by BRENDA team
Liu, X.; Sturla, S.J.
Profiling patterns of glutathione reductase inhibition by the natural product illudin S and its acylfulvene analogues
Mol. Biosyst.
5
1013-1024
2009
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Kedrowski, B.L.; Gutow, J.H.; Stock, G.; Smith, M.; Jordan, C.; Masterson, D.S.
Glutathione reductase activity with an oxidized methylated glutathione analog
J. Enzyme Inhib. Med. Chem.
29
491-494
2014
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Murakami, K.; Tsubouchi, R.; Fukayama, M.; Yoshino, M.
Copper-dependent inhibition and oxidative inactivation with affinity cleavage of yeast glutathione reductase
Biometals
27
551-558
2014
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Couto, N.; Malys, N.; Gaskell, S.J.; Barber, J.
Partition and turnover of glutathione reductase from Saccharomyces cerevisiae a proteomic approach
J. Proteome Res.
12
2885-2894
2013
Saccharomyces cerevisiae, Saccharomyces cerevisiae BY4742
Manually annotated by BRENDA team
Horn, T.; Bettray, W.; Slusarenko, A.; Gruhlke, M.
S-Allylmercaptoglutathione is a substrate for glutathione reductase (E.C. 1.8.1.7) from yeast (Saccharomyces cerevisiae)
Antioxidants (Basel)
7
86
2018
Saccharomyces cerevisiae, Saccharomyces cerevisiae BY4742
Manually annotated by BRENDA team
Dalmizrak, O.; Terali, K.; Abdullah, R.K.; Ozer, N.
Mechanistic and structural insights into the in vitro inhibitory action of hypericin on glutathione reductase purified from bakers yeast
J. Biochem. Mol. Toxicol.
32
e22051
2018
Saccharomyces cerevisiae (P41921), Saccharomyces cerevisiae, Saccharomyces cerevisiae ATCC 204508 (P41921)
Manually annotated by BRENDA team