EzCatDB: T00213
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DB codeT00213
CATH domainDomain 13.50.50.60 : FAD/NAD(P)-binding domainCatalytic domain
Domain 23.50.50.60 : FAD/NAD(P)-binding domainCatalytic domain
Domain 33.30.390.30 : Enolase-like; domain 1Catalytic domain
E.C.1.8.1.7
CSA1get
MACiEM0006

CATH domainRelated DB codes (homologues)
3.30.390.30 : Enolase-like; domain 1M00163,T00017,T00233,T00242
3.50.50.60 : FAD/NAD(P)-binding domainM00163,D00015,D00041,D00042,D00045,D00064,D00071,T00004,T00015,T00017,T00025,T00211,T00233,T00242

Enzyme Name
UniProtKBKEGG

P06715P41921Q94655P00390
Protein nameGlutathione reductaseGlutathione reductaseGlutathione reductaseGlutathione reductase, mitochondrialglutathione-disulfide reductase
glutathione reductase
glutathione reductase (NADPH)
NADPH-glutathione reductase
GSH reductase
GSSG reductase
NADPH-GSSG reductase
glutathione S-reductase
NADPH:oxidized-glutathione oxidoreductase
SynonymsGRase
GR
EC 1.8.1.7
GRase
GR
EC 1.8.1.7
GRase
GR
EC 1.8.1.7
GRase
GR
EC 1.8.1.7
RefSeqNP_417957.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_491935.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
NP_015234.1 (Protein)
NM_001183905.1 (DNA/RNA sequence)

NP_000628.2 (Protein)
NM_000637.3 (DNA/RNA sequence)
NP_001182031.1 (Protein)
NM_001195102.1 (DNA/RNA sequence)
NP_001182032.1 (Protein)
NM_001195103.1 (DNA/RNA sequence)
NP_001182033.1 (Protein)
NM_001195104.1 (DNA/RNA sequence)
PfamPF00070 (Pyr_redox)
PF07992 (Pyr_redox_2)
PF02852 (Pyr_redox_dim)
[Graphical view]
PF00070 (Pyr_redox)
PF07992 (Pyr_redox_2)
PF02852 (Pyr_redox_dim)
[Graphical view]
PF00070 (Pyr_redox)
PF07992 (Pyr_redox_2)
PF02852 (Pyr_redox_dim)
[Graphical view]
PF00070 (Pyr_redox)
PF07992 (Pyr_redox_2)
PF02852 (Pyr_redox_dim)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00251Glutamate metabolism
MAP00480Glutathione metabolism

UniProtKB:Accession NumberP06715P41921Q94655P00390
Entry nameGSHR_ECOLIGSHR_YEASTGSHR_PLAFKGSHR_HUMAN
Activity2 glutathione + NADP(+) = glutathione disulfide + NADPH.2 glutathione + NADP(+) = glutathione disulfide + NADPH.2 glutathione + NADP(+) = glutathione disulfide + NADPH.2 glutathione + NADP(+) = glutathione disulfide + NADPH.
SubunitHomodimer.
Homodimer.Homodimer, disulfide-linked.
Subcellular locationCytoplasm.Cytoplasm (By similarity).Cytoplasm.Mitochondrion. Cytoplasm.
CofactorBinds 1 FAD per subunit.Binds 1 FAD per subunit (By similarity).Binds 1 FAD per subunit (By similarity).Binds 1 FAD per subunit.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProductsintermediates
KEGG-idC00016C00127C00005C00080C00051C00006
CompoundFADOxidized glutathioneNADPHH+GlutathioneNADP+glutathione-covalently-bound to Cys
Typeamide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,nucleotideamino acids,carboxyl group,peptide/protein,disulfide bondamide group,amine group,nucleotideothersamino acids,carboxyl group,peptide/protein,sulfhydryl groupamide group,amine group,nucleotide
ChEBI16238
17858
16474
15378
16856
18009

PubChem643975
65359
11215652
5884
1038
25246407
124886
5886

               
1gerA01Bound:FADUnboundUnbound UnboundUnboundUnbound
1gerB01Bound:FADUnboundUnbound UnboundUnboundUnbound
1gesA01Bound:FADUnboundUnbound UnboundUnboundUnbound
1gesB01Bound:FADUnboundUnbound UnboundUnboundUnbound
1getA01Bound:FADUnboundUnbound UnboundUnboundUnbound
1getB01Bound:FADUnboundUnbound UnboundUnboundUnbound
1geuA01Bound:FADUnboundUnbound UnboundUnboundUnbound
1geuB01Bound:FADUnboundUnbound UnboundUnboundUnbound
2hqmA01Bound:FADUnboundUnbound UnboundUnboundUnbound
2hqmB01Bound:FADUnboundUnbound UnboundUnboundUnbound
1onfA01Bound:FADUnboundUnbound UnboundUnboundUnbound
1bwcA01Bound:FADUnboundUnbound Analogue:AJ3UnboundUnbound
1dncA01Bound:FADUnboundUnbound UnboundUnboundIntermediate-bound:GTT-CYS 58
1graA01Bound:FADBound:GSH-GSHUnbound UnboundUnboundUnbound
1grbA01Bound:FADUnboundUnbound UnboundUnboundUnbound
1greA01Bound:FADUnboundUnbound Bound:GSH 482UnboundIntermediate-bound:GSH 481-CYS 58
1grfA01Bound:FADUnboundUnbound UnboundUnboundIntermediate-analogue:ACM-CYS 58
1grgA01Bound:FADUnboundUnbound UnboundUnboundIntermediate-analogue:CEC-CYS 58
1grtA01Bound:FADUnboundUnbound UnboundUnboundUnbound
1gsnA01Bound:FADUnboundUnbound UnboundUnboundIntermediate-bound:GTT-CYS 58
1xanA01Bound:FADUnboundUnbound UnboundUnboundUnbound
2aaqA01Bound:FADUnboundUnbound UnboundUnboundUnbound
2gh5A01Bound:FADUnboundUnbound UnboundUnboundIntermediate-analogue:ELI-CYS 58
2gh5B01Bound:FADUnboundUnbound UnboundUnboundIntermediate-analogue:ELI-CYS 58
2grtA01Bound:FADBound:GDSUnbound UnboundUnboundUnbound
3grsA01Bound:FADUnboundUnbound UnboundUnboundUnbound
3grtA01Bound:FADAnalogue:TS2Unbound UnboundUnboundUnbound
4gr1A01Bound:FADAnalogue:RGSUnbound UnboundUnboundUnbound
4grtA01Bound:FADUnboundUnbound UnboundUnboundIntermediate-analogue:GCG-CYS 58
5grtA01Bound:FADAnalogue:TS4Unbound UnboundUnboundUnbound
1gerA02UnboundUnboundUnbound UnboundUnboundUnbound
1gerB02UnboundUnboundUnbound UnboundUnboundUnbound
1gesA02UnboundUnboundUnbound UnboundUnboundUnbound
1gesB02UnboundUnboundUnbound UnboundUnboundUnbound
1getA02UnboundUnboundUnbound UnboundBound:NAPUnbound
1getB02UnboundUnboundUnbound UnboundBound:NAPUnbound
1geuA02UnboundUnboundUnbound UnboundAnalogue:NADUnbound
1geuB02UnboundUnboundUnbound UnboundAnalogue:NADUnbound
2hqmA02UnboundUnboundUnbound UnboundUnboundUnbound
2hqmB02UnboundUnboundUnbound UnboundUnboundUnbound
1onfA02UnboundUnboundUnbound UnboundUnboundUnbound
1bwcA02UnboundUnboundUnbound UnboundUnboundUnbound
1dncA02UnboundUnboundUnbound UnboundUnboundUnbound
1graA02UnboundUnboundAnalogue:NDP UnboundUnboundUnbound
1grbA02UnboundUnboundBound:NDP UnboundAnalogue:NADUnbound
1greA02UnboundUnboundUnbound UnboundUnboundUnbound
1grfA02UnboundUnboundUnbound UnboundUnboundUnbound
1grgA02UnboundUnboundUnbound UnboundUnboundUnbound
1grtA02UnboundUnboundUnbound UnboundUnboundUnbound
1gsnA02UnboundUnboundUnbound UnboundUnboundUnbound
1xanA02UnboundUnboundUnbound UnboundUnboundUnbound
2aaqA02UnboundUnboundUnbound UnboundUnboundUnbound
2gh5A02UnboundUnboundUnbound UnboundUnboundUnbound
2gh5B02UnboundUnboundUnbound UnboundUnboundUnbound
2grtA02UnboundUnboundUnbound UnboundUnboundUnbound
3grsA02UnboundUnboundUnbound UnboundUnboundUnbound
3grtA02UnboundUnboundUnbound UnboundUnboundUnbound
4gr1A02UnboundUnboundUnbound UnboundUnboundUnbound
4grtA02UnboundUnboundUnbound UnboundUnboundUnbound
5grtA02UnboundUnboundUnbound UnboundUnboundUnbound
1gerA03UnboundUnboundUnbound UnboundUnboundUnbound
1gerB03UnboundUnboundUnbound UnboundUnboundUnbound
1gesA03UnboundUnboundUnbound UnboundUnboundUnbound
1gesB03UnboundUnboundUnbound UnboundUnboundUnbound
1getA03UnboundUnboundUnbound UnboundUnboundUnbound
1getB03UnboundUnboundUnbound UnboundUnboundUnbound
1geuA03UnboundUnboundUnbound UnboundUnboundUnbound
1geuB03UnboundUnboundUnbound UnboundUnboundUnbound
2hqmA03UnboundUnboundUnbound UnboundUnboundUnbound
2hqmB03UnboundUnboundUnbound UnboundUnboundUnbound
1onfA03UnboundUnboundUnbound UnboundUnboundUnbound
1bwcA03UnboundUnboundUnbound UnboundUnboundUnbound
1dncA03UnboundUnboundUnbound UnboundUnboundUnbound
1graA03UnboundUnboundUnbound UnboundUnboundUnbound
1grbA03UnboundUnboundUnbound UnboundUnboundUnbound
1greA03UnboundUnboundUnbound UnboundUnboundUnbound
1grfA03UnboundUnboundUnbound UnboundUnboundUnbound
1grgA03UnboundUnboundUnbound UnboundUnboundUnbound
1grtA03UnboundUnboundUnbound UnboundUnboundUnbound
1gsnA03UnboundUnboundUnbound UnboundUnboundUnbound
1xanA03UnboundUnboundUnbound UnboundUnboundUnbound
2aaqA03UnboundUnboundUnbound UnboundUnboundUnbound
2gh5A03UnboundUnboundUnbound UnboundUnboundUnbound
2gh5B03UnboundUnboundUnbound UnboundUnboundUnbound
2grtA03UnboundUnboundUnbound UnboundUnboundUnbound
3grsA03UnboundUnboundUnbound UnboundUnboundUnbound
3grtA03UnboundUnboundUnbound UnboundUnboundUnbound
4gr1A03UnboundUnboundUnbound UnboundUnboundUnbound
4grtA03UnboundUnboundUnbound UnboundUnboundUnbound
5grtA03UnboundUnboundUnbound UnboundUnboundUnbound

Active-site residues
resource
PDB;2grt & Swiss-prot;P06715, P00390 & literature [7], [9], [16], [39], [46]
pdbCatalytic residuesModified residuescomment
           
1gerA01CYS 42;CYS 47;LYS 50
 
disulfide bonded/oxidized form C42-C47
1gerB01CYS 42;CYS 47;LYS 50
 
disulfide bonded/oxidized form C42-C47
1gesA01CYS 42;CYS 47;LYS 50
 
disulfide bonded/oxidized form C42-C47
1gesB01CYS 42;CYS 47;LYS 50
 
disulfide bonded/oxidized form C42-C47
1getA01CYS 42;CYS 47;LYS 50
 
reduced form C42, C47
1getB01CYS 42;CYS 47;LYS 50
 
reduced form C42, C47
1geuA01CYS 42;CYS 47;LYS 50
 
reduced form C42, C47
1geuB01CYS 42;CYS 47;LYS 50
 
reduced form C42, C47
2hqmA01CYS 61;CYS 66;LYS 69
 
disulfide bonded/oxidized form C61-C66
2hqmB01CYS 61;CYS 66;LYS 69
 
disulfide bonded/oxidized form C61-C66
1onfA01CYS 39;CYS 44;LYS 47
 
reduced form C39, C44
1bwcA01CYS 58;CYS 63;LYS 66
 
disulfide bonded/oxidized form C58-C63
1dncA01CYS 58;      ;LYS 66
CSD 63(sulfinylated)
modified C63
1graA01CYS 58;CYS 63;LYS 66
 
disulfide bonded/oxidized form C58-C63
1grbA01CYS 58;CYS 63;LYS 66
 
reduced form C58, C63
1greA01CYS 58;CYS 63;LYS 66
 
 
1grfA01CYS 58;CYS 63;LYS 66
 
 
1grgA01CYS 58;CYS 63;LYS 66
 
 
1grtA01CYS 58;CYS 63;LYS 66
 
mutant A34E, R37W, disulfide bonded/oxidized form C58-C63
1gsnA01CYS 58;      ;LYS 66
CSO 63(sulfenylated)
 
1xanA01CYS 58;CYS 63;LYS 66
 
disulfide bonded/oxidized form C58-C63
2aaqA01CYS 58;CYS 63;LYS 66
 
reduced form C58, C63
2gh5A01CYS 58;CYS 63;LYS 66
 
 
2gh5B01CYS 58;CYS 63;LYS 66
 
 
2grtA01CYS 58;CYS 63;LYS 66
 
mutant A34E, R37W, disulfide bonded/oxidized form C58-C63
3grsA01CYS 58;CYS 63;LYS 66
 
disulfide bonded/oxidized form C58-C63
3grtA01CYS 58;CYS 63;LYS 66
 
mutant A34E, R37W, disulfide bonded/oxidized form C58-C63
4gr1A01CYS 58;CYS 63;LYS 66
 
disulfide bonded/oxidized form C58-C63
4grtA01CYS 58;CYS 63;LYS 66
 
mutant A34E, R37W
5grtA01CYS 58;CYS 63;LYS 66
 
mutant A34E, R37W, disulfide bonded/oxidized form C58-C63
1gerA02TYR 177;GLU 181
 
 
1gerB02TYR 177;GLU 181
 
 
1gesA02TYR 177;GLU 181
 
mutant A179G, A183G, V197E, R198M, K199F, H200D, R204P
1gesB02TYR 177;GLU 181
 
mutant A179G, A183G, V197E, R198M, K199F, H200D, R204P
1getA02TYR 177;GLU 181
 
 
1getB02TYR 177;GLU 181
 
 
1geuA02TYR 177;GLU 181
 
mutant A179G, A183G, V197E, R198M, K199F, H200D, R204P
1geuB02TYR 177;GLU 181
 
mutant A179G, A183G, V197E, R198M, K199F, H200D, R204P
2hqmA02TYR 207;GLU 211
 
 
2hqmB02TYR 207;GLU 211
 
 
1onfA02TYR 185;GLU 189
 
 
1bwcA02TYR 197;GLU 201
 
 
1dncA02TYR 197;GLU 201
 
 
1graA02TYR 197;GLU 201
 
 
1grbA02TYR 197;GLU 201
 
 
1greA02TYR 197;GLU 201
 
 
1grfA02TYR 197;GLU 201
 
 
1grgA02TYR 197;GLU 201
 
 
1grtA02TYR 197;GLU 201
 
 
1gsnA02TYR 197;GLU 201
CSO 234(sulfenylated);CSO 284(sulfenylated)
 
1xanA02TYR 197;GLU 201
 
 
2aaqA02TYR 197;GLU 201
 
 
2gh5A02TYR 197;GLU 201
 
 
2gh5B02TYR 197;GLU 201
 
 
2grtA02TYR 197;GLU 201
 
 
3grsA02TYR 197;GLU 201
 
 
3grtA02TYR 197;GLU 201
 
 
4gr1A02TYR 197;GLU 201
 
 
4grtA02TYR 197;GLU 201
 
 
5grtA02TYR 197;GLU 201
 
 
1gerA03HIS 439;GLU 444
 
 
1gerB03HIS 439;GLU 444
 
 
1gesA03HIS 439;GLU 444
 
 
1gesB03HIS 439;GLU 444
 
 
1getA03HIS 439;GLU 444
 
 
1getB03HIS 439;GLU 444
 
 
1geuA03HIS 439;GLU 444
 
 
1geuB03HIS 439;GLU 444
 
 
2hqmA03HIS 472;GLU 477
 
 
2hqmB03HIS 472;GLU 477
 
 
1onfA03HIS 484;GLU 489
 
 
1bwcA03HIS 467;GLU 472
 
 
1dncA03HIS 467;GLU 472
 
 
1graA03HIS 467;GLU 472
 
 
1grbA03HIS 467;GLU 472
 
 
1greA03HIS 467;GLU 472
 
 
1grfA03HIS 467;GLU 472
 
 
1grgA03HIS 467;GLU 472
 
 
1grtA03HIS 467;GLU 472
 
 
1gsnA03HIS 467;GLU 472
CSO 423(sulfenylated)
 
1xanA03HIS 467;GLU 472
 
 
2aaqA03HIS 467;GLU 472
 
 
2gh5A03HIS 467;GLU 472
 
 
2gh5B03HIS 467;GLU 472
 
 
2grtA03HIS 467;GLU 472
 
 
3grsA03HIS 467;GLU 472
 
 
3grtA03HIS 467;GLU 472
 
 
4gr1A03HIS 467;GLU 472
 
 
4grtA03HIS 467;GLU 472
 
 
5grtA03HIS 467;GLU 472
 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]p.301-304
[3]Fig.5, p.1754-1757
[4]Fig.6, p.376-377
[5]p.495
[7]p.342-343
[9]p.725-728
[11]Fig.1, p.315
[13]Fig.1, p.9602-9603
[16]Fig.1, p.175-179
[17]Fig.6, p.4028-4029
[40]p.13972-13975, p.13976-13977
[48]Scheme 3
[53]p.900
[55]p.10784-10785, Scheme 1, Scheme 2

references
[1]
CommentsX-RAY CRYSTALLOGRAPHY (2 ANGSTROMS) OF 45-522
Medline ID82145544
PubMed ID7334521
JournalJ Mol Biol
Year1981
Volume152
Pages763-82
AuthorsThieme R, Pai EF, Schirmer RH, Schulz GE
TitleThree-dimensional structure of glutathione reductase at 2 A resolution.
Related UniProtKBP00390
[2]
PubMed ID7175934
JournalJ Mol Biol
Year1982
Volume160
Pages287-308
AuthorsSchulz GE, Schirmer RH, Pai EF
TitleFAD-binding site of glutathione reductase.
[3]
PubMed ID6822532
JournalJ Biol Chem
Year1983
Volume258
Pages1752-7
AuthorsPai EF, Schulz GE
TitleThe catalytic mechanism of glutathione reductase as derived from x-ray diffraction analyses of reaction intermediates.
[4]
PubMed ID6697994
JournalEur J Biochem
Year1984
Volume138
Pages373-8
AuthorsBilzer M, Krauth-Siegel RL, Schirmer RH, Akerboom TP, Sies H, Schulz GE
TitleInteraction of a glutathione S-conjugate with glutathione reductase. Kinetic and X-ray crystallographic studies.
[5]
PubMed ID6546954
JournalJ Mol Biol
Year1984
Volume174
Pages483-96
AuthorsRice DW, Schulz GE, Guest JR
TitleStructural relationship between glutathione reductase and lipoamide dehydrogenase.
[6]
PubMed ID3885856
JournalArch Biochem Biophys
Year1985
Volume238
Pages213-8
AuthorsHuber PW, Brandt KG
TitleKinetic studies of the reduction of yeast glutathione reductase by reduced nicotinamide hypoxanthine dinucleotide phosphate.
[7]
PubMed ID3987692
JournalEur J Biochem
Year1985
Volume148
Pages335-44
AuthorsKrauth-Siegel RL, Schirmer RH, Ghisla S
TitleFAD analogues as prosthetic groups of human glutathione reductase. Properties of the modified enzyme species and comparisons with the active site structure.
[8]
PubMed ID3581436
JournalCell Biochem Funct
Year1987
Volume5
Pages79-95
AuthorsRosemeyer MA
TitleThe biochemistry of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and glutathione reductase.
[9]
CommentsX-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 45-522
Medline ID88011277
PubMed ID3656429
JournalJ Mol Biol
Year1987
Volume195
Pages701-29
AuthorsKarplus PA, Schulz GE
TitleRefined structure of glutathione reductase at 1.54 A resolution.
Related PDB3grs
Related UniProtKBP00390
[10]
PubMed ID2844232
JournalBiochemistry
Year1988
Volume27
Pages4465-74
AuthorsPai EF, Karplus PA, Schulz GE
TitleCrystallographic analysis of the binding of NADPH, NADPH fragments, and NADPH analogues to glutathione reductase.
[11]
PubMed ID3338461
JournalEur J Biochem
Year1988
Volume171
Pages193-8
AuthorsKarplus PA, Krauth-Siegel RL, Schirmer RH, Schulz GE
TitleInhibition of human glutathione reductase by the nitrosourea drugs 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-(2-hydroxyethyl)-1-nitrosourea. A crystallographic analysis.
[12]
PubMed ID2666188
JournalBiochem Soc Trans
Year1989
Volume17
Pages315-7
AuthorsKrauth-Siegel RL, Jockers-Scherubl MC, Becker K, Schirmer RH
TitleNADPH-dependent disulphide reductases.
[13]
PubMed ID2558727
JournalBiochemistry
Year1989
Volume28
Pages9602-7
AuthorsDeonarain MP, Berry A, Scrutton NS, Perham RN
TitleAlternative proton donors/acceptors in the catalytic mechanism of the glutathione reductase of Escherichia coli: the role of histidine-439 and tyrosine-99.
[14]
PubMed ID2647141
JournalBiochim Biophys Acta
Year1989
Volume973
Pages399-404
AuthorsCenas NK, Rakauskiene GA, Kulys JJ
TitleOne- and two-electron reduction of quinones by glutathione reductase.
[15]
PubMed ID2912729
JournalEur J Biochem
Year1989
Volume178
Pages693-703
AuthorsKarplus PA, Pai EF, Schulz GE
TitleA crystallographic study of the glutathione binding site of glutathione reductase at 0.3-nm resolution.
[16]
CommentsX-ray crystallography
PubMed ID2585516
JournalJ Mol Biol
Year1989
Volume210
Pages163-80
AuthorsKarplus PA, Schulz GE
TitleSubstrate binding and catalysis by glutathione reductase as derived from refined enzyme: substrate crystal structures at 2 A resolution.
Related PDB1gra,1grb,1gre,1grf,1grg
[17]
PubMed ID2354175
JournalBiochemistry
Year1990
Volume29
Pages4022-30
AuthorsJanes W, Schulz GE
TitleRole of the charged groups of glutathione disulfide in the catalysis of glutathione reductase: crystallographic and kinetic studies with synthetic analogues.
[18]
PubMed ID2176163
JournalFEBS Lett
Year1990
Volume276
Pages189-91
AuthorsShi XL, Dalal NS
TitleNADPH-dependent flavoenzymes catalyze one electron reduction of metal ions and molecular oxygen and generate hydroxyl radicals.
[19]
CommentsX-ray crystallography
PubMed ID2355009
JournalJ Biol Chem
Year1990
Volume265
Pages10443-5
AuthorsJanes W, Schulz GE
TitleThe binding of the retro-analogue of glutathione disulfide to glutathione reductase.
Related PDB4gr1
[20]
CommentsX-ray crystallography
PubMed ID2059620
JournalBiochemistry
Year1991
Volume30
Pages6124-7
AuthorsBradley M, Bucheler US, Walsh CT
TitleRedox enzyme engineering: conversion of human glutathione reductase into a trypanothione reductase.
Related PDB3grt
[21]
PubMed ID2065668
JournalEur J Biochem
Year1991
Volume199
Pages133-8
AuthorsErmler U, Ghisla S, Massey V, Schulz GE
TitleStructural, spectroscopic and catalytic activity studies on glutathione reductase reconstituted with FAD analogues.
[22]
PubMed ID1880807
JournalJ Mol Biol
Year1991
Volume220
Pages975-94
AuthorsMattevi A, Schierbeek AJ, Hol WG
TitleRefined crystal structure of lipoamide dehydrogenase from Azotobacter vinelandii at 2.2 A resolution. A comparison with the structure of glutathione reductase.
[23]
PubMed ID2067578
JournalNature
Year1991
Volume352
Pages172-4
AuthorsKuriyan J, Krishna TS, Wong L, Guenther B, Pahler A, Williams CH Jr, Model P
TitleConvergent evolution of similar function in two structurally divergent enzymes.
[24]
PubMed ID1924337
JournalProc Natl Acad Sci U S A
Year1991
Volume88
Pages8769-73
AuthorsHenderson GB, Murgolo NJ, Kuriyan J, Osapay K, Kominos D, Berry A, Scrutton NS, Hinchliffe NW, Perham RN, Cerami A
TitleEngineering the substrate specificity of glutathione reductase toward that of trypanothione reduction.
[25]
CommentsX-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS)
Medline ID91172742
PubMed ID2006135
JournalProteins
Year1991
Volume9
Pages174-9
AuthorsErmler U, Schulz GE
TitleThe three-dimensional structure of glutathione reductase from Escherichia coli at 3.0 A resolution.
Related UniProtKBP06715
[26]
PubMed ID1524433
JournalArch Biochem Biophys
Year1992
Volume298
Pages247-53
AuthorsLibreros-Minotta CA, Pardo JP, Mendoza-Hernandez G, Rendon JL
TitlePurification and characterization of glutathione reductase from Rhodospirillum rubrum.
[27]
PubMed ID8510142
JournalJ Mol Biol
Year1993
Volume231
Pages191-5
AuthorsMittl PR, Berry A, Scrutton NS, Perham RN, Schulz GE
TitleStructural differences between wild-type NADP-dependent glutathione reductase from Escherichia coli and a redesigned NAD-dependent mutant.
[28]
CommentsX-ray crystallography
PubMed ID7833810
JournalProtein Sci
Year1994
Volume3
Pages1504-14
AuthorsMittl PR, Berry A, Scrutton NS, Perham RN, Schulz GE
TitleAnatomy of an engineered NAD-binding site.
Related PDB1ges,1get,1geu
[29]
CommentsX-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS)
Medline ID94339840
PubMed ID8061609
JournalProtein Sci
Year1994
Volume3
Pages799-809
AuthorsMittl PR, Schulz GE
TitleStructure of glutathione reductase from Escherichia coli at 1.86 A resolution: comparison with the enzyme from human erythrocytes.
Related PDB1ger
Related UniProtKBP06715
[30]
PubMed ID8526866
JournalBiochem J
Year1995
Volume312
Pages527-33
AuthorsBashir A, Perham RN, Scrutton NS, Berry A
TitleAltering kinetic mechanism and enzyme stability by mutagenesis of the dimer interface of glutathione reductase.
[31]
PubMed ID7499374
JournalJ Biol Chem
Year1995
Volume270
Pages28586-94
AuthorsMurthy YV, Massey V
TitleChemical modification of the N-10 ribityl side chain of flavins. Effects on properties of flavoprotein disulfide oxidoreductases.
[32]
PubMed ID8739033
JournalBiochem Mol Biol Int
Year1996
Volume38
Pages1117-26
AuthorsPaulikova H, Petrickova I, Antalik M, Podhradsky D
TitleEffect of heparin and dextran sulfate on the activity of glutathione reductase from yeast.
[33]
CommentsX-ray crystallography
PubMed ID8626496
JournalJ Biol Chem
Year1996
Volume271
Pages8101-7
AuthorsSavvides SN, Karplus PA
TitleKinetics and crystallographic analysis of human glutathione reductase in complex with a xanthene inhibitor.
Related PDB1xan
[34]
PubMed ID8691487
JournalJ Med Chem
Year1996
Volume39
Pages1549-54
AuthorsSchonleben-Janas A, Kirsch P, Mittl PR, Schirmer RH, Krauth-Siegel RL
TitleInhibition of human glutathione reductase by 10-arylisoalloxazines: crystalline, kinetic, and electrochemical studies.
[35]
PubMed ID8631352
JournalEur J Biochem
Year1996
Volume235
Pages345-50
AuthorsKrauth-Siegel RL, M?ller JG, Lottspeich F, Schirmer RH
TitleGlutathione reductase and glutamate dehydrogenase of Plasmodium falciparum, the causative agent of tropical malaria.
Related UniProtKBQ94655
[36]
CommentsX-ray crystallography
PubMed ID9174360
JournalBiochemistry
Year1997
Volume36
Pages6437-47
AuthorsStoll VS, Simpson SJ, Krauth-Siegel RL, Walsh CT, Pai EF
TitleGlutathione reductase turned into trypanothione reductase: structural analysis of an engineered change in substrate specificity.
Related PDB1grt,2grt,4grt,5grt
[37]
CommentsNMR structure
PubMed ID9151953
JournalEur J Biochem
Year1997
Volume245
Pages273-82
AuthorsNordhoff A, Tziatzios C, van den Broek JA, Schott MK, Kalbitzer HR, Becker K, Schubert D, Schirmer RH
TitleDenaturation and reactivation of dimeric human glutathione reductase--an assay for folding inhibitors.
Related PDB1alg
[38]
PubMed ID9268306
JournalJ Biol Chem
Year1997
Volume272
Pages21767-73
AuthorsBoese M, Keese MA, Becker K, Busse R, Mulsch A
TitleInhibition of glutathione reductase by dinitrosyl-iron-dithiolate complex.
[39]
PubMed ID9247856
JournalJ Enzyme Inhib
Year1997
Volume12
Pages143-54
AuthorsPandey A, Iyengar L, Katiyar SS
TitleModification of an essential amino group of glutathione reductase from yeast by pyridoxal 5'-phosphate.
[40]
PubMed ID9760231
JournalBiochemistry
Year1998
Volume37
Pages13968-77
AuthorsKrauth-Siegel RL, Arscott LD, Schonleben-Janas A, Schirmer RH, Williams CH Jr
TitleRole of active site tyrosine residues in catalysis by human glutathione reductase.
[41]
PubMed ID9799522
JournalBiochemistry
Year1998
Volume37
Pages15575-82
AuthorsVeine DM, Arscott LD, Williams CH Jr
TitleRedox potentials for yeast, Escherichia coli and human glutathione reductase relative to the NAD+/NADH redox couple: enzyme forms active in catalysis.
[42]
PubMed ID9545063
JournalBiophys J
Year1998
Volume74
Pages2046-58
Authorsvan den Berg PA, van Hoek A, Walentas CD, Perham RN, Visser AJ
TitleFlavin fluorescence dynamics and photoinduced electron transfer in Escherichia coli glutathione reductase.
[43]
PubMed ID9535831
JournalJ Biol Chem
Year1998
Volume273
Pages8581-91
AuthorsZhong L, Arn-er ES, Ljung J, Aslund F, Holmgren A
TitleRat and calf thioredoxin reductase are homologous to glutathione reductase with a carboxyl-terminal elongation containing a conserved catalytically active penultimate selenocysteine residue.
[44]
CommentsX-ray crystallography
PubMed ID9546215
JournalNat Struct Biol
Year1998
Volume5
Pages267-71
AuthorsBecker K, Savvides SN, Keese M, Schirmer RH, Karplus PA
TitleEnzyme inactivation through sulfhydryl oxidation by physiologic NO-carriers.
Related PDB1dnc,1gsn
[45]
PubMed ID10413499
JournalBiochemistry
Year1999
Volume38
Pages9254-63
AuthorsDanielson UH, Jiang F, Hansson LO, Mannervik B
TitleProbing the kinetic mechanism and coenzyme specificity of glutathione reductase from the cyanobacterium Anabaena PCC 7120 by redesign of the pyridine-nucleotide-binding site.
[46]
PubMed ID10094686
JournalJ Bacteriol
Year1999
Volume181
Pages2094-101
Authorsvan Hylckama Vlieg JE, Kingma J, Kruizinga W, Janssen DB
TitlePurification of a glutathione S-transferase and a glutathione conjugate-specific dehydrogenase involved in isoprene metabolism in Rhodococcus sp. strain AD45.
[47]
CommentsX-ray crystallography
PubMed ID9986706
JournalJ Med Chem
Year1999
Volume42
Pages364-72
AuthorsGallwitz H, Bonse S, Martinez-Cruz A, Schlichting I, Schumacher K, Krauth-Siegel RL
TitleAjoene is an inhibitor and subversive substrate of human glutathione reductase and Trypanosoma cruzi trypanothione reductase: crystallographic, kinetic, and spectroscopic studies.
Related PDB1bwc
[48]
PubMed ID10769127
JournalBiochemistry
Year2000
Volume39
Pages4711-21
AuthorsArscott LD, Veine DM, Williams CH Jr
TitleMixed disulfide with glutathione as an intermediate in the reaction catalyzed by glutathione reductase from yeast and as a major form of the enzyme in the cell.
[49]
PubMed ID10779594
JournalMol Biochem Parasitol
Year2000
Volume107
Pages169-79
AuthorsGilberger TW, Schirmer RH, Walter RD, Muller S
TitleDeletion of the parasite-specific insertions and mutation of the catalytic triad in glutathione reductase from chloroquine-sensitive Plasmodium falciparum 3D7.
[50]
PubMed ID11370850
JournalArch Biochem Biophys
Year2001
Volume387
Pages265-72
AuthorsRendon JL, Mendoza-Hernandez G
TitleUnfolding kinetics of glutathione reductase from cyanobacterium Spirulina maxima.
[51]
PubMed ID11705998
JournalJ Biol Chem
Year2002
Volume277
Pages2779-84
AuthorsSavvides SN, Scheiwein M, Bohme CC, Arteel GE, Karplus PA, Becker K, Schirmer RH
TitleCrystal structure of the antioxidant enzyme glutathione reductase inactivated by peroxynitrite.
[52]
PubMed ID12111385
JournalJ Mol Model (Online)
Year2002
Volume8
Pages173-83
AuthorsIribarne F, Paulino M, Aguilera S, Murphy M, Tapia O
TitleDocking and molecular dynamics studies at trypanothione reductase and glutathione reductase active sites.
[53]
PubMed ID12729762
JournalJ Mol Biol
Year2003
Volume328
Pages893-907
AuthorsSarma GN, Savvides SN, Becker K, Schirmer M, Schirmer RH, Karplus PA
TitleGlutathione reductase of the malarial parasite Plasmodium falciparum: crystal structure and inhibitor development.
Related PDB1onf
[54]
PubMed ID16493712
JournalAngew Chem Int Ed Engl
Year2006
Volume45
Pages1881-6
AuthorsUrig S, Fritz-Wolf K, R?au R, Herold-Mende C, T?th K, Davioud-Charvet E, Becker K
TitleUndressing of phosphine gold(I) complexes as irreversible inhibitors of human disulfide reductases.
Related PDB2aaq
[55]
PubMed ID16910673
JournalJ Am Chem Soc
Year2006
Volume128
Pages10784-94
AuthorsBauer H, Fritz-Wolf K, Winzer A, K?hner S, Little S, Yardley V, Vezin H, Palfey B, Schirmer RH, Davioud-Charvet E
TitleA fluoro analogue of the menadione derivative 6-[2'-(3'-methyl)-1',4'-naphthoquinolyl]hexanoic acid is a suicide substrate of glutathione reductase. Crystal structure of the alkylated human enzyme.
Related PDB2gh5
[56]
PubMed ID17554778
JournalProteins
Year2007
Volume68
Pages972-9
AuthorsYu J, Zhou CZ
TitleCrystal structure of glutathione reductase Glr1 from the yeast Saccharomyces cerevisiae.
Related PDB2hqm

comments
This enzyme was transferred from E.C. 1.6.4.2 to E.C. 1.8.1.7.
This enzyme catalyzes the following reactions (see [3], [13], [16]):
(A) Hydride or electron transfer from NADPH to FAD, forming FADH2 (Reduction of FAD by NADPH):
(A0) This hydride transfer involves Glu201, Lys 66 and Tyr197.
(B) Electron transfer from FADH2 to redox-active disulfide bond Cys63-Cys58 (oxidized form), forming reduced form of cysteine residues:
(B1) The C4a atom of flavin (FADH2) makes a nucleophilic attack on the sulfur atom of Cys63, causing Cys58 to leave as a thiolate ion (SN2-like reaction).
(B2) This reaction proceeds via a short-lived (unstable) intermediate (covalent bond between C4a of flavin and sulfur atom of Cys63).
(B3) The fate of the transferred hydrogen on the flavin is not clear (see [16]).
(C) Electron transfer from Cys58 (and Cys63) to glutathione disulfide (or oxidized glutathione, GSSG), producing two glutathione molecules (GSH) (see [3], [16]):
(C0) Glu472 modulates the pKa of His467'. Moreover, Tyr114 might assist His467' (see [40]).
(C1) His467' acts as a general base to deprotonate the sulfur of Cys58.
(C2) Cys58 makes a nucleophilic attack on the Cys-I of GSSG, forming a mixed disulfide bond between C58 and GSH-I, and causing Cys-II to leave as a thiolate ion. (During this reaction, electrons shift from Cys58 to Cys-I.)
(C2') The protonated sidechain of His467' polarizes the mixed disulfide bond.
(C3) Cys63 makes a nucleophilic attack on the Cys58, forming a disulfide bond again, and causing Cys-I to leave as a thiolate ion. Here, His467' acts as a general acid to protonate the thiolate of Cys-I.

createdupdated
2004-12-222009-02-26
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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