EzCatDB: D00045
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DB codeD00045
CATH domainDomain 13.50.50.60 : FAD/NAD(P)-binding domain
Domain 23.50.50.60 : FAD/NAD(P)-binding domainCatalytic domain
E.C.1.8.1.9
CSA1tde

CATH domainRelated DB codes (homologues)
3.50.50.60 : FAD/NAD(P)-binding domainM00163,D00015,D00041,D00042,D00064,D00071,T00004,T00015,T00017,T00025,T00211,T00213,T00233,T00242

Enzyme Name
UniProtKBKEGG

Q39243P0A9P4
Protein nameThioredoxin reductase 1Thioredoxin reductasethioredoxin-disulfide reductase
NADP-thioredoxin reductase
NADPH-thioredoxin reductase
thioredoxin reductase (NADPH)
NADPH2:oxidized thioredoxin oxidoreductase
SynonymsEC 1.8.1.9
NADPH-dependent thioredoxin reductase 1
NTR 1
TRXR
EC 1.8.1.9
RefSeqNP_195271.2 (Protein)
NM_119711.3 (DNA/RNA sequence)
NP_415408.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_489160.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
PfamPF00070 (Pyr_redox)
PF07992 (Pyr_redox_2)
[Graphical view]
PF00070 (Pyr_redox)
PF07992 (Pyr_redox_2)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00240Pyrimidine metabolism

UniProtKB:Accession NumberQ39243P0A9P4
Entry nameTRXB1_ARATHTRXB_ECOLI
ActivityThioredoxin + NADP(+) = thioredoxin disulfide + NADPH.Thioredoxin + NADP(+) = thioredoxin disulfide + NADPH.
SubunitHomodimer.Homodimer.
Subcellular locationCytoplasm.Cytoplasm.
CofactorBinds 1 FAD per subunit.Binds 1 FAD per subunit.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00016C00005C00343C00080C00006C00342
CompoundFADNADPHOxidized thioredoxinH+NADP+Reduced thioredoxin
Typeamide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,nucleotideamide group,amine group,nucleotideamide group,carbohydrate,disulfide bond,peptide/proteinothersamide group,amine group,nucleotideamide group,carbohydrate,peptide/protein,sulfhydryl group
ChEBI16238
16474

15378
18009

PubChem643975
5884

1038
5886

              
1cl0A01Bound:FADUnboundUnbound UnboundUnbound
1f6mA01Bound:FADUnboundUnbound UnboundUnbound
1f6mB01Bound:FADUnboundUnbound UnboundUnbound
1f6mE01Bound:FADUnboundUnbound UnboundUnbound
1f6mF01Bound:FADUnboundUnbound UnboundUnbound
1tdeA01Bound:FADUnboundUnbound UnboundUnbound
1tdfA01Bound:FADUnboundUnbound UnboundUnbound
1trbA01Bound:FADUnboundUnbound UnboundUnbound
1vdcA01Bound:FADUnboundUnbound UnboundUnbound
1cl0A02UnboundUnboundUnbound UnboundUnbound
1f6mA02UnboundUnboundUnbound Analogue:3AAAnalogue:CYS 32-SER 35(chain C)
1f6mB02UnboundUnboundUnbound Analogue:3AAAnalogue:CYS 32-SER 35(chain D)
1f6mE02UnboundUnboundUnbound Analogue:3AAAnalogue:CYS 32-SER 35(chain G)
1f6mF02UnboundUnboundUnbound Analogue:3AAAnalogue:CYS 32-SER 35(chain H)
1tdeA02UnboundUnboundUnbound UnboundUnbound
1tdfA02UnboundUnboundUnbound Bound:NAPUnbound
1trbA02UnboundUnboundUnbound UnboundUnbound
1vdcA02UnboundUnboundUnbound UnboundUnbound

Active-site residues
resource
PDB;1vdc & literature [6]
pdbCatalytic residuescomment
          
1cl0A01 
 
1f6mA01 
 
1f6mB01 
 
1f6mE01 
 
1f6mF01 
 
1tdeA01 
 
1tdfA01 
 
1trbA01 
 
1vdcA01 
 
1cl0A02CYS 135;CYS 138;ASP 139
 
1f6mA02       ;CYS 138;ASP 139
mutant C135S
1f6mB02       ;CYS 138;ASP 139
mutant C135S
1f6mE02       ;CYS 138;ASP 139
mutant C135S
1f6mF02       ;CYS 138;ASP 139
mutant C135S
1tdeA02CYS 135;CYS 138;ASP 139
 
1tdfA02CYS 135;       ;ASP 139
mutant C138S
1trbA02CYS 135;       ;ASP 139
mutant C138S
1vdcA02CYS 135;CYS 138;ASP 139
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[4]p.3153
[6]p.810, p.813-815
[7]Scheme 1, Scheme 2, Scheme 3, p.1271-1275
[8]Fig.1, Scheme 1, Scheme 2, p.4708-4711
[11]Scheme 1, p.373-374
[12]Fig.1, Fig.2, p.2370-2373, p.2375
[16]Fig.1
[17]Fig.1

references
[1]
PubMed ID2666412
JournalJ Biol Chem
Year1989
Volume264
Pages12752-3
AuthorsKuriyan J, Wong L, Russel M, Model P
TitleCrystallization and preliminary x-ray characterization of thioredoxin reductase from Escherichia coli.
[2]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS)
Medline ID91296031
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.
Related PDB1trb
Related UniProtKBP0A9P4
[3]
PubMed ID8440680
JournalJ Biol Chem
Year1993
Volume268
Pages3845-9
AuthorsNikkola M, Gleason FK, Eklund H
TitleReduction of mutant phage T4 glutaredoxins by Escherichia coli thioredoxin reductase.
[4]
PubMed ID8136348
JournalBiochemistry
Year1994
Volume33
Pages3148-54
AuthorsMulrooney SB, Williams CH Jr
TitlePotential active-site base of thioredoxin reductase from Escherichia coli: examination of histidine245 and aspartate139 by site-directed mutagenesis.
[5]
PubMed ID7989308
JournalJ Biol Chem
Year1994
Volume269
Pages31418-23
AuthorsOhnishi K, Niimura Y, Yokoyama K, Hidaka M, Masaki H, Uchimura T, Suzuki H, Uozumi T, Kozaki M, Komagata K, et al
TitlePurification and analysis of a flavoprotein functional as NADH oxidase from Amphibacillus xylanus overexpressed in Escherichia coli.
[6]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS)
Medline ID94157914
PubMed ID8114095
JournalJ Mol Biol
Year1994
Volume236
Pages800-16
AuthorsWaksman G, Krishna TS, Williams CH Jr, Kuriyan J
TitleCrystal structure of Escherichia coli thioredoxin reductase refined at 2 A resolution. Implications for a large conformational change during catalysis.
Related PDB1tde,1tdf
Related UniProtKBP0A9P4
[7]
PubMed ID7557016
JournalFASEB J
Year1995
Volume9
Pages1267-76
AuthorsWilliams CH Jr
TitleMechanism and structure of thioredoxin reductase from Escherichia coli.
[8]
PubMed ID8664260
JournalBiochemistry
Year1996
Volume35
Pages4704-12
AuthorsLennon BW, Williams CH Jr
TitleEnzyme-monitored turnover of Escherichia coli thioredoxin reductase: insights for catalysis.
[9]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS)
Medline ID97153339
PubMed ID9000629
JournalJ Mol Biol
Year1996
Volume264
Pages1044-57
AuthorsDai S, Saarinen M, Ramaswamy S, Meyer Y, Jacquot JP, Eklund H
TitleCrystal structure of Arabidopsis thaliana NADPH dependent thioredoxin reductase at 2.5 A resolution.
Related PDB1vdc
Related UniProtKBQ39243
[10]
PubMed ID9482874
JournalProc Natl Acad Sci U S A
Year1998
Volume95
Pages2267-72
AuthorsSvergun DI, Richard S, Koch MH, Sayers Z, Kuprin S, Zaccai G
TitleProtein hydration in solution: experimental observation by x-ray and neutron scattering.
[11]
PubMed ID9521113
JournalProtein Sci
Year1998
Volume7
Pages369-75
AuthorsVeine DM, Ohnishi K, Williams CH Jr
TitleThioredoxin reductase from Escherichia coli: evidence of restriction to a single conformation upon formation of a crosslink between engineered cysteines.
[12]
CommentsX-RAY CRYSTALLOGRAPHY
Medline ID20060988
PubMed ID10595539
JournalProtein Sci
Year1999
Volume8
Pages2366-79
AuthorsLennon BW, Williams CH Jr, Ludwig ML
TitleCrystal structure of reduced thioredoxin reductase from Escherichia coli: structural flexibility in the isoalloxazine ring of the flavin adenine dinucleotide cofactor.
Related PDB1cl0
Related UniProtKBP0A9P4
[13]
PubMed ID10913298
JournalBiochemistry
Year2000
Volume39
Pages8859-69
AuthorsReynolds CM, Poole LB
TitleAttachment of the N-terminal domain of Salmonella typhimurium AhpF to Escherichia coli thioredoxin reductase confers AhpC reductase activity but does not affect thioredoxin reductase activity.
[14]
PubMed ID10984401
JournalBiopolymers
Year2000
Volume54
Pages489-500
AuthorsRenner C, Behrendt R, Sporlein S, Wachtveitl J, Moroder L
TitlePhotomodulation of conformational states. I. Mono- and bicyclic peptides with (4-amino)phenylazobenzoic acid as backbone constituent.
[15]
PubMed ID10984402
JournalBiopolymers
Year2000
Volume54
Pages501-14
AuthorsRenner C, Cramer J, Behrendt R, Moroder L
TitlePhotomodulation of conformational states. II. Mono- and bicyclic peptides with (4-aminomethyl)phenylazobenzoic acid as backbone constituent.
[16]
PubMed ID11012662
JournalEur J Biochem
Year2000
Volume267
Pages6110-7
AuthorsWilliams CH, Arscott LD, Muller S, Lennon BW, Ludwig ML, Wang PF, Veine DM, Becker K, Schirmer RH
TitleThioredoxin reductase two modes of catalysis have evolved.
[17]
CommentsX-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) IN COMPLEX WITH TRXA
Medline ID20407464
PubMed ID10947986
JournalScience
Year2000
Volume289
Pages1190-4
AuthorsLennon BW, Williams CH Jr, Ludwig ML
TitleTwists in catalysis: alternating conformations of Escherichia coli thioredoxin reductase.
Related PDB1f6m
Related UniProtKBP0A9P4
[18]
PubMed ID11567095
JournalProtein Sci
Year2001
Volume10
Pages2037-49
Authorsvan den Berg PA, Mulrooney SB, Gobets B, van Stokkum IH, van Hoek A, Williams CH Jr, Visser AJ
TitleExploring the conformational equilibrium of E. coli thioredoxin reductase: characterization of two catalytically important states by ultrafast flavin fluorescence spectroscopy.
[19]
PubMed ID12079785
JournalChem Biol
Year2002
Volume9
Pages731-40
AuthorsCabrele C, Fiori S, Pegoraro S, Moroder L
TitleRedox-active cyclic bis(cysteinyl)peptides as catalysts for in vitro oxidative protein folding.
[20]
PubMed ID12379950
JournalTrends Parasitol
Year2002
Volume18
Pages302-8
AuthorsHirt RP, Muller S, Embley TM, Coombs GH
TitleThe diversity and evolution of thioredoxin reductase: new perspectives.

comments
There are two distinct types in thioredoxin reductase: large one (mammalian, Plasmodium falciparum) and small one (bacteria, plant) (see [16]). This enzyme corresponds to the small one.
This enzyme catalyzes three distinct redox reactions;
(A) Hydride or electron transfer from NADPH to FAD (Reduction of FAD by NADPH) (part of reductive half-reaction)
(B) Electron transfer from reduced FAD (FADH2) to active-site disulfide (Cys135-Cys138)(part of reductive half-reaction)
(C) Electron transfer from active site cysteine residues to thioredoxin substrate (Reduction of substrate (thioredoxin) at the active site)
There are two active sites in this enzyme.
(a) Active site composed of Cys135/Cys138/Asp139: involved in reactions (B) & (C)
(b) Active site with Glu159: involved in reaction (A)
PDB structure 1f6m suggests the reactions (A) & (C), whilst the other structures indicate the reaction (B).

createdupdated
2004-03-242009-02-26


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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)
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