TYTR_TRYCR
ID TYTR_TRYCR Reviewed; 492 AA.
AC P28593;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 142.
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 cruzi.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Trypanosoma; Schizotrypanum.
OX NCBI_TaxID=5693;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2011150; DOI=10.1016/0166-6851(91)90231-t;
RA Sullivan F.X., Walsh C.T.;
RT "Cloning, sequencing, overproduction and purification of trypanothione
RT reductase from Trypanosoma cruzi.";
RL Mol. Biochem. Parasitol. 44:145-148(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Silvio;
RX PubMed=7737173; DOI=10.1111/j.1432-1033.1995.tb20319.x;
RA Borges A., Cunningham M.L., Tover J., Fairlamb A.H.;
RT "Site-directed mutagenesis of the redox-active cysteines of Trypanosoma
RT cruzi trypanothione reductase.";
RL Eur. J. Biochem. 228:745-752(1995).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 2-492, AND DISULFIDE BOND.
RX PubMed=8428618; DOI=10.1016/0014-5793(93)81501-p;
RA Krauth-Siegel R.L., Sticherling C., Jost I., Walsh C.T., Pai E.F.,
RA Kabsch W., Lantwin C.B.;
RT "Crystallization and preliminary crystallographic analysis of trypanothione
RT reductase from Trypanosoma cruzi, the causative agent of Chagas' disease.";
RL FEBS Lett. 317:105-108(1993).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS).
RX PubMed=8159665; DOI=10.1002/prot.340180208;
RA Lantwin C.B., Schlichting I., Kabsch W., Pai E.F., Krauth-Siegel R.L.;
RT "The structure of Trypanosoma cruzi trypanothione reductase in the oxidized
RT and NADPH reduced state.";
RL Proteins 18:161-173(1994).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RC STRAIN=Silvio;
RX PubMed=8771196; DOI=10.1002/pro.5560050107;
RA Zhang Y., Bond C.S., Bailey S., Cunningham M.L., Fairlamb A.H.,
RA Hunter W.N.;
RT "The crystal structure of trypanothione reductase from the human pathogen
RT Trypanosoma cruzi at 2.3-A resolution.";
RL Protein Sci. 5:52-61(1996).
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;
CC Note=Binds 1 FAD per subunit.;
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; M38051; AAA63547.1; -; Genomic_DNA.
DR EMBL; Z13958; CAA78360.1; -; Genomic_DNA.
DR PIR; S68968; S68968.
DR PDB; 1AOG; X-ray; 2.30 A; A/B=3-487.
DR PDB; 1BZL; X-ray; 2.40 A; A/B=2-487.
DR PDB; 1GXF; X-ray; 2.70 A; A/B=1-492.
DR PDB; 1NDA; X-ray; 3.30 A; A/B/C/D=2-492.
DR PDBsum; 1AOG; -.
DR PDBsum; 1BZL; -.
DR PDBsum; 1GXF; -.
DR PDBsum; 1NDA; -.
DR AlphaFoldDB; P28593; -.
DR SMR; P28593; -.
DR BindingDB; P28593; -.
DR ChEMBL; CHEMBL5131; -.
DR DrugBank; DB03147; Flavin adenine dinucleotide.
DR DrugBank; DB04299; Maleic acid.
DR DrugBank; DB02240; Quinacrine mustard.
DR DrugBank; DB03470; Trypanothione.
DR DrugCentral; P28593; -.
DR VEuPathDB; TriTrypDB:BCY84_10688; -.
DR VEuPathDB; TriTrypDB:C3747_19g298; -.
DR VEuPathDB; TriTrypDB:C4B63_14g241; -.
DR VEuPathDB; TriTrypDB:Tc_MARK_3549; -.
DR VEuPathDB; TriTrypDB:TcBrA4_0014700; -.
DR VEuPathDB; TriTrypDB:TcCL_ESM09797; -.
DR VEuPathDB; TriTrypDB:TcCLB.503555.30; -.
DR VEuPathDB; TriTrypDB:TcCLB.504507.5; -.
DR VEuPathDB; TriTrypDB:TCDM_11669; -.
DR VEuPathDB; TriTrypDB:TcG_08092; -.
DR VEuPathDB; TriTrypDB:TCSYLVIO_004807; -.
DR VEuPathDB; TriTrypDB:TcYC6_0175630; -.
DR BRENDA; 1.8.1.12; 6524.
DR EvolutionaryTrace; P28593; -.
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 3D-structure; Cytoplasm; Disulfide bond; FAD; Flavoprotein; NADP;
KW Oxidoreductase; Redox-active center.
FT CHAIN 1..492
FT /note="Trypanothione reductase"
FT /id="PRO_0000067992"
FT ACT_SITE 461
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 36..52
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT DISULFID 53..58
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:8428618"
FT VARIANT 95
FT /note="K -> N (in strain: Silvio)"
FT VARIANT 140
FT /note="E -> A (in strain: Silvio)"
FT VARIANT 156
FT /note="N -> H (in strain: Silvio)"
FT VARIANT 353
FT /note="N -> T (in strain: Silvio)"
FT VARIANT 402..403
FT /note="NI -> KV (in strain: Silvio)"
FT VARIANT 441
FT /note="V -> I (in strain: Silvio)"
FT STRAND 5..11
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 15..26
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 32..37
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 39..42
FT /evidence="ECO:0007829|PDB:1AOG"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 51..56
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 58..76
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 77..80
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 93..117
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 121..132
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 135..143
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 148..155
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 173..175
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 179..182
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 190..195
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 199..211
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 217..228
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 233..245
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 249..253
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 256..261
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 267..271
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 276..284
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 293..295
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 297..299
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 306..309
FT /evidence="ECO:0007829|PDB:1BZL"
FT STRAND 322..324
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 326..329
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 335..350
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 351..353
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 364..366
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 372..376
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 379..385
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 387..396
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 399..404
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 411..418
FT /evidence="ECO:0007829|PDB:1AOG"
FT TURN 419..421
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 423..431
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 434..446
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 451..455
FT /evidence="ECO:0007829|PDB:1AOG"
FT HELIX 465..469
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 475..479
FT /evidence="ECO:0007829|PDB:1AOG"
FT STRAND 482..484
FT /evidence="ECO:0007829|PDB:1AOG"
SQ SEQUENCE 492 AA; 53868 MW; 4AF179952A20750F CRC64;
MMSKIFDLVV IGAGSGGLEA AWNAATLYKK RVAVIDVQMV HGPPFFSALG GTCVNVGCVP
KKLMVTGAQY MEHLRESAGF GWEFDRTTLR AEWKKLIAVK DEAVLNINKS YEEMFRDTEG
LEFFLGWGSL ESKNVVNVRE SADPASAVKE RLETENILLA SGSWPHMPNI PGIEHCISSN
EAFYLPEPPR RVLTVGGGFI SVEFAGIFNA YKPKDGQVTL CYRGEMILRG FDHTLREELT
KQLTANGIQI LTKENPAKVE LNADGSKSVT FESGKKMDFD LVMMAIGRSP RTKDLQLQNA
GVMIKNGGVQ VDEYSRTNVS NIYAIGDVTN RVMLTPVAIN EAAALVDTVF GTNPRKTDHT
RVASAVFSIP PIGTCGLIEE VASKRYEVVA VYLSSFTPLM HNISGSKYKT FVAKIITNHS
DGTVLGVHLL GDNAPEIIQG VGICLKLNAK ISDFYNTIGV HPTSAEELCS MRTPSYYYVK
GEKMEKPSEA SL
