ID   TYTR_TRYCO              Reviewed;         492 AA.
AC   P13110;
DT   01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1990, sequence version 1.
DT   03-AUG-2022, entry version 127.
DE   RecName: Full=Trypanothione reductase;
DE            Short=TR;
DE            EC=1.8.1.12;
DE   AltName: Full=N(1),N(8)-bis(glutathionyl)spermidine reductase;
GN   Name=TPR;
OS   Trypanosoma congolense.
OC   Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC   Trypanosomatida; Trypanosomatidae; Trypanosoma; Nannomonas.
OX   NCBI_TaxID=5692;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3167026; DOI=10.1021/bi00414a010;
RA   Shames S.L., Kimmel B.E., Peoples O.P., Agabian N., Walsh C.T.;
RT   "Trypanothione reductase of Trypanosoma congolense: gene isolation, primary
RT   sequence determination, and comparison to glutathione reductase.";
RL   Biochemistry 27:5014-5019(1988).
RN   [2]
RP   REVIEW.
RX   PubMed=1957352; DOI=10.1016/0968-0004(91)90124-e;
RA   Walsh C.T., Bradley M., Nadeau K.;
RT   "Molecular studies on trypanothione reductase, a target for antiparasitic
RT   drugs.";
RL   Trends Biochem. Sci. 16:305-309(1991).
CC   -!- FUNCTION: Trypanothione is the parasite analog of glutathione; this
CC       enzyme is the equivalent of glutathione reductase.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=NADP(+) + trypanothione = H(+) + NADPH + trypanothione
CC         disulfide; Xref=Rhea:RHEA:16757, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58290, ChEBI:CHEBI:58349,
CC         ChEBI:CHEBI:58661; EC=1.8.1.12;
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC       Note=Binds 1 FAD per subunit. {ECO:0000250};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=18 uM for trypanothione;
CC   -!- SUBUNIT: Homodimer.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- MISCELLANEOUS: The active site is a redox-active disulfide bond.
CC   -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC       oxidoreductase family. {ECO:0000305}.
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DR   EMBL; M21122; AAA30258.1; -; Genomic_DNA.
DR   PIR; A27727; A27727.
DR   AlphaFoldDB; P13110; -.
DR   SMR; P13110; -.
DR   VEuPathDB; TriTrypDB:TcIL3000.A.H_000810800; -.
DR   VEuPathDB; TriTrypDB:TcIL3000_10_8870; -.
DR   SABIO-RK; P13110; -.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR   GO; GO:0015042; F:trypanothione-disulfide reductase activity; IEA:UniProtKB-EC.
DR   GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
DR   Gene3D; 3.30.390.30; -; 1.
DR   Gene3D; 3.50.50.60; -; 2.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   InterPro; IPR023753; FAD/NAD-binding_dom.
DR   InterPro; IPR016156; FAD/NAD-linked_Rdtase_dimer_sf.
DR   InterPro; IPR001100; Pyr_nuc-diS_OxRdtase.
DR   InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
DR   InterPro; IPR012999; Pyr_OxRdtase_I_AS.
DR   InterPro; IPR001864; Trypnth_redctse.
DR   Pfam; PF07992; Pyr_redox_2; 1.
DR   Pfam; PF02852; Pyr_redox_dim; 1.
DR   PIRSF; PIRSF000350; Mercury_reductase_MerA; 1.
DR   PRINTS; PR00470; TRYPANRDTASE.
DR   SUPFAM; SSF51905; SSF51905; 1.
DR   SUPFAM; SSF55424; SSF55424; 1.
DR   TIGRFAMs; TIGR01423; trypano_reduc; 1.
DR   PROSITE; PS00076; PYRIDINE_REDOX_1; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; Disulfide bond; FAD; Flavoprotein; NADP; Oxidoreductase;
KW   Redox-active center.
FT   CHAIN           1..492
FT                   /note="Trypanothione reductase"
FT                   /id="PRO_0000067991"
FT   ACT_SITE        461
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         35..52
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   DISULFID        52..57
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000250"
FT   MUTAGEN         18
FT                   /note="E->A: KM=266 uM for trypanothione."
FT   MUTAGEN         21
FT                   /note="W->R: KM=600 uM for trypanothione."
FT   MUTAGEN         343
FT                   /note="A->R: KM=9 uM for trypanothione."
SQ   SEQUENCE   492 AA;  53443 MW;  48F305A4C8C09685 CRC64;
     MSKAFDLVII GAGSGGLEAG WNAATLYKKR VAVVDVQTVH GPPFFAALGG TCVNVGCVPK
     KLMVTGAQYM DQLRESAGFG WEFDASTIKA NWKTLIAAKN AAVLDINKSY EDMFKDTEGL
     EFFLGWGALE QKNVVTVREG ADPKSKVKER LQAEHIIIAT GSWPQMLKIP GIEHCISSNE
     AFYLEEPPRR VLTVGGGFIS VEFAGIFNAY KPVGGKVTLC YRNNPILRGF DYTLRQELTK
     QLVANGIDIM TNENPSKIEL NPDGSKHVTF ESGKTLDVDV VMMAIGRLPR TGYLQLQTVG
     VNLTDKGAIQ VDEFSRTNVP NIYAIGDVTG RIMLTPVAIN EGASVVDTIF GSKPRKTDHT
     RVASAVFSIP PIGTCGLTEE EAAKSFEKVA VYLSCFTPLM HNISGSKYKK FVAKIITDHG
     DGTVVGVHLL GDSSPEIIQA VGICMKLNAK ISDFYNTIGV HPTSAEELCS MRTPSHYYIK
     GEKMETLPDS SL