EzCatDB: T00213

DB codeT00213
CATH domainDomain 13.50.50.60Catalytic domain
Domain 23.50.50.60Catalytic domain
Domain 33.30.390.30Catalytic domain
E.C.1.8.1.7
CSA1get

CATH domainRelated DB codes (homologues)
3.30.390.30M00163,T00017,T00233,T00242
3.50.50.60M00163,D00015,D00041,D00042,D00045,D00064,D00071,T00004,T00015,T00017,T00025,T00211,T00233,T00242

Enzyme Name
Swiss-protKEGG

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

KEGG pathways
MAP codePathways
MAP00251Glutamate metabolism
MAP00480Glutathione metabolism

Swiss-prot: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.


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
1gerA1Bound:FADUnboundUnbound
UnboundUnboundUnbound
1gerB1Bound:FADUnboundUnbound
UnboundUnboundUnbound
1gesA1Bound:FADUnboundUnbound
UnboundUnboundUnbound
1gesB1Bound:FADUnboundUnbound
UnboundUnboundUnbound
1getA1Bound:FADUnboundUnbound
UnboundUnboundUnbound
1getB1Bound:FADUnboundUnbound
UnboundUnboundUnbound
1geuA1Bound:FADUnboundUnbound
UnboundUnboundUnbound
1geuB1Bound:FADUnboundUnbound
UnboundUnboundUnbound
2hqmA1Bound:FADUnboundUnbound
UnboundUnboundUnbound
2hqmB1Bound:FADUnboundUnbound
UnboundUnboundUnbound
1onfA1Bound:FADUnboundUnbound
UnboundUnboundUnbound
1bwcA1Bound:FADUnboundUnbound
Analogue:AJ3UnboundUnbound
1dncA1Bound:FADUnboundUnbound
UnboundUnboundIntermediate-bound:GTT-CYS 58
1graA1Bound:FADBound:GSH-GSHUnbound
UnboundUnboundUnbound
1grbA1Bound:FADUnboundUnbound
UnboundUnboundUnbound
1greA1Bound:FADUnboundUnbound
Bound:GSH 482UnboundIntermediate-bound:GSH 481-CYS 58
1grfA1Bound:FADUnboundUnbound
UnboundUnboundIntermediate-analogue:ACM-CYS 58
1grgA1Bound:FADUnboundUnbound
UnboundUnboundIntermediate-analogue:CEC-CYS 58
1grtA1Bound:FADUnboundUnbound
UnboundUnboundUnbound
1gsnA1Bound:FADUnboundUnbound
UnboundUnboundIntermediate-bound:GTT-CYS 58
1xanA1Bound:FADUnboundUnbound
UnboundUnboundUnbound
2aaqA1Bound:FADUnboundUnbound
UnboundUnboundUnbound
2gh5A1Bound:FADUnboundUnbound
UnboundUnboundIntermediate-analogue:ELI-CYS 58
2gh5B1Bound:FADUnboundUnbound
UnboundUnboundIntermediate-analogue:ELI-CYS 58
2grtA1Bound:FADBound:GDSUnbound
UnboundUnboundUnbound
3grsA1Bound:FADUnboundUnbound
UnboundUnboundUnbound
3grtA1Bound:FADAnalogue:TS2Unbound
UnboundUnboundUnbound
4gr1A1Bound:FADAnalogue:RGSUnbound
UnboundUnboundUnbound
4grtA1Bound:FADUnboundUnbound
UnboundUnboundIntermediate-analogue:GCG-CYS 58
5grtA1Bound:FADAnalogue:TS4Unbound
UnboundUnboundUnbound
1gerA2UnboundUnboundUnbound
UnboundUnboundUnbound
1gerB2UnboundUnboundUnbound
UnboundUnboundUnbound
1gesA2UnboundUnboundUnbound
UnboundUnboundUnbound
1gesB2UnboundUnboundUnbound
UnboundUnboundUnbound
1getA2UnboundUnboundUnbound
UnboundBound:NAPUnbound
1getB2UnboundUnboundUnbound
UnboundBound:NAPUnbound
1geuA2UnboundUnboundUnbound
UnboundAnalogue:NADUnbound
1geuB2UnboundUnboundUnbound
UnboundAnalogue:NADUnbound
2hqmA2UnboundUnboundUnbound
UnboundUnboundUnbound
2hqmB2UnboundUnboundUnbound
UnboundUnboundUnbound
1onfA2UnboundUnboundUnbound
UnboundUnboundUnbound
1bwcA2UnboundUnboundUnbound
UnboundUnboundUnbound
1dncA2UnboundUnboundUnbound
UnboundUnboundUnbound
1graA2UnboundUnboundAnalogue:NDP
UnboundUnboundUnbound
1grbA2UnboundUnboundBound:NDP
UnboundAnalogue:NADUnbound
1greA2UnboundUnboundUnbound
UnboundUnboundUnbound
1grfA2UnboundUnboundUnbound
UnboundUnboundUnbound
1grgA2UnboundUnboundUnbound
UnboundUnboundUnbound
1grtA2UnboundUnboundUnbound
UnboundUnboundUnbound
1gsnA2UnboundUnboundUnbound
UnboundUnboundUnbound
1xanA2UnboundUnboundUnbound
UnboundUnboundUnbound
2aaqA2UnboundUnboundUnbound
UnboundUnboundUnbound
2gh5A2UnboundUnboundUnbound
UnboundUnboundUnbound
2gh5B2UnboundUnboundUnbound
UnboundUnboundUnbound
2grtA2UnboundUnboundUnbound
UnboundUnboundUnbound
3grsA2UnboundUnboundUnbound
UnboundUnboundUnbound
3grtA2UnboundUnboundUnbound
UnboundUnboundUnbound
4gr1A2UnboundUnboundUnbound
UnboundUnboundUnbound
4grtA2UnboundUnboundUnbound
UnboundUnboundUnbound
5grtA2UnboundUnboundUnbound
UnboundUnboundUnbound
1gerA3UnboundUnboundUnbound
UnboundUnboundUnbound
1gerB3UnboundUnboundUnbound
UnboundUnboundUnbound
1gesA3UnboundUnboundUnbound
UnboundUnboundUnbound
1gesB3UnboundUnboundUnbound
UnboundUnboundUnbound
1getA3UnboundUnboundUnbound
UnboundUnboundUnbound
1getB3UnboundUnboundUnbound
UnboundUnboundUnbound
1geuA3UnboundUnboundUnbound
UnboundUnboundUnbound
1geuB3UnboundUnboundUnbound
UnboundUnboundUnbound
2hqmA3UnboundUnboundUnbound
UnboundUnboundUnbound
2hqmB3UnboundUnboundUnbound
UnboundUnboundUnbound
1onfA3UnboundUnboundUnbound
UnboundUnboundUnbound
1bwcA3UnboundUnboundUnbound
UnboundUnboundUnbound
1dncA3UnboundUnboundUnbound
UnboundUnboundUnbound
1graA3UnboundUnboundUnbound
UnboundUnboundUnbound
1grbA3UnboundUnboundUnbound
UnboundUnboundUnbound
1greA3UnboundUnboundUnbound
UnboundUnboundUnbound
1grfA3UnboundUnboundUnbound
UnboundUnboundUnbound
1grgA3UnboundUnboundUnbound
UnboundUnboundUnbound
1grtA3UnboundUnboundUnbound
UnboundUnboundUnbound
1gsnA3UnboundUnboundUnbound
UnboundUnboundUnbound
1xanA3UnboundUnboundUnbound
UnboundUnboundUnbound
2aaqA3UnboundUnboundUnbound
UnboundUnboundUnbound
2gh5A3UnboundUnboundUnbound
UnboundUnboundUnbound
2gh5B3UnboundUnboundUnbound
UnboundUnboundUnbound
2grtA3UnboundUnboundUnbound
UnboundUnboundUnbound
3grsA3UnboundUnboundUnbound
UnboundUnboundUnbound
3grtA3UnboundUnboundUnbound
UnboundUnboundUnbound
4gr1A3UnboundUnboundUnbound
UnboundUnboundUnbound
4grtA3UnboundUnboundUnbound
UnboundUnboundUnbound
5grtA3UnboundUnboundUnbound
UnboundUnboundUnbound

Active-site residues
resource
PDB;2grt & Swiss-prot;P06715, P00390 & literature [7], [9], [16], [39], [46]
pdbCatalytic residuesModified residuescomment
1gerA1CYS 42;CYS 47;LYS 50

disulfide bonded/oxidized form C42-C47
1gerB1CYS 42;CYS 47;LYS 50

disulfide bonded/oxidized form C42-C47
1gesA1CYS 42;CYS 47;LYS 50

disulfide bonded/oxidized form C42-C47
1gesB1CYS 42;CYS 47;LYS 50

disulfide bonded/oxidized form C42-C47
1getA1CYS 42;CYS 47;LYS 50

reduced form C42, C47
1getB1CYS 42;CYS 47;LYS 50

reduced form C42, C47
1geuA1CYS 42;CYS 47;LYS 50

reduced form C42, C47
1geuB1CYS 42;CYS 47;LYS 50

reduced form C42, C47
2hqmA1CYS 61;CYS 66;LYS 69

disulfide bonded/oxidized form C61-C66
2hqmB1CYS 61;CYS 66;LYS 69

disulfide bonded/oxidized form C61-C66
1onfA1CYS 39;CYS 44;LYS 47

reduced form C39, C44
1bwcA1CYS 58;CYS 63;LYS 66

disulfide bonded/oxidized form C58-C63
1dncA1CYS 58;      ;LYS 66
CSD 63(sulfinylated)
modified C63
1graA1CYS 58;CYS 63;LYS 66

disulfide bonded/oxidized form C58-C63
1grbA1CYS 58;CYS 63;LYS 66

reduced form C58, C63
1greA1CYS 58;CYS 63;LYS 66


1grfA1CYS 58;CYS 63;LYS 66


1grgA1CYS 58;CYS 63;LYS 66


1grtA1CYS 58;CYS 63;LYS 66

mutant A34E, R37W, disulfide bonded/oxidized form C58-C63
1gsnA1CYS 58;      ;LYS 66
CSO 63(sulfenylated)

1xanA1CYS 58;CYS 63;LYS 66

disulfide bonded/oxidized form C58-C63
2aaqA1CYS 58;CYS 63;LYS 66

reduced form C58, C63
2gh5A1CYS 58;CYS 63;LYS 66


2gh5B1CYS 58;CYS 63;LYS 66


2grtA1CYS 58;CYS 63;LYS 66

mutant A34E, R37W, disulfide bonded/oxidized form C58-C63
3grsA1CYS 58;CYS 63;LYS 66

disulfide bonded/oxidized form C58-C63
3grtA1CYS 58;CYS 63;LYS 66

mutant A34E, R37W, disulfide bonded/oxidized form C58-C63
4gr1A1CYS 58;CYS 63;LYS 66

disulfide bonded/oxidized form C58-C63
4grtA1CYS 58;CYS 63;LYS 66

mutant A34E, R37W
5grtA1CYS 58;CYS 63;LYS 66

mutant A34E, R37W, disulfide bonded/oxidized form C58-C63
1gerA2TYR 177;GLU 181


1gerB2TYR 177;GLU 181


1gesA2TYR 177;GLU 181

mutant A179G, A183G, V197E, R198M, K199F, H200D, R204P
1gesB2TYR 177;GLU 181

mutant A179G, A183G, V197E, R198M, K199F, H200D, R204P
1getA2TYR 177;GLU 181


1getB2TYR 177;GLU 181


1geuA2TYR 177;GLU 181

mutant A179G, A183G, V197E, R198M, K199F, H200D, R204P
1geuB2TYR 177;GLU 181

mutant A179G, A183G, V197E, R198M, K199F, H200D, R204P
2hqmA2TYR 207;GLU 211


2hqmB2TYR 207;GLU 211


1onfA2TYR 185;GLU 189


1bwcA2TYR 197;GLU 201


1dncA2TYR 197;GLU 201


1graA2TYR 197;GLU 201


1grbA2TYR 197;GLU 201


1greA2TYR 197;GLU 201


1grfA2TYR 197;GLU 201


1grgA2TYR 197;GLU 201


1grtA2TYR 197;GLU 201


1gsnA2TYR 197;GLU 201
CSO 234(sulfenylated);CSO 284(sulfenylated)

1xanA2TYR 197;GLU 201


2aaqA2TYR 197;GLU 201


2gh5A2TYR 197;GLU 201


2gh5B2TYR 197;GLU 201


2grtA2TYR 197;GLU 201


3grsA2TYR 197;GLU 201


3grtA2TYR 197;GLU 201


4gr1A2TYR 197;GLU 201


4grtA2TYR 197;GLU 201


5grtA2TYR 197;GLU 201


1gerA3HIS 439;GLU 444


1gerB3HIS 439;GLU 444


1gesA3HIS 439;GLU 444


1gesB3HIS 439;GLU 444


1getA3HIS 439;GLU 444


1getB3HIS 439;GLU 444


1geuA3HIS 439;GLU 444


1geuB3HIS 439;GLU 444


2hqmA3HIS 472;GLU 477


2hqmB3HIS 472;GLU 477


1onfA3HIS 484;GLU 489


1bwcA3HIS 467;GLU 472


1dncA3HIS 467;GLU 472


1graA3HIS 467;GLU 472


1grbA3HIS 467;GLU 472


1greA3HIS 467;GLU 472


1grfA3HIS 467;GLU 472


1grgA3HIS 467;GLU 472


1grtA3HIS 467;GLU 472


1gsnA3HIS 467;GLU 472
CSO 423(sulfenylated)

1xanA3HIS 467;GLU 472


2aaqA3HIS 467;GLU 472


2gh5A3HIS 467;GLU 472


2gh5B3HIS 467;GLU 472


2grtA3HIS 467;GLU 472


3grsA3HIS 467;GLU 472


3grtA3HIS 467;GLU 472


4gr1A3HIS 467;GLU 472


4grtA3HIS 467;GLU 472


5grtA3HIS 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 Swiss-protP00390
[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 Swiss-protP00390
[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 Swiss-protP06715
[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 Swiss-protP06715
[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 Swiss-protQ94655
[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/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 BIRD/Japan Science and Technology Corporation (JST) (September 2005-)

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