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 10-JUN-2026, entry version 151. 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=trypanothione + NADP(+) = trypanothione disulfide + NADPH + CC H(+); Xref=Rhea:RHEA:16757, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58290, ChEBI:CHEBI:58349, 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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:ECC02_012776; -. 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:0005829; C:cytosol; IEA:TreeGrafter. DR GO; GO:0005739; C:mitochondrion; IEA:TreeGrafter. DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro. DR GO; GO:0004362; F:glutathione-disulfide reductase (NADPH) activity; IEA:TreeGrafter. DR GO; GO:0015042; F:trypanothione-disulfide reductase (NADPH) activity; IEA:UniProtKB-EC. DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro. DR GO; GO:0034599; P:cellular response to oxidative stress; IEA:TreeGrafter. DR GO; GO:0006749; P:glutathione metabolic process; IEA:TreeGrafter. DR FunFam; 3.50.50.60:FF:000051; Glutathione reductase; 1. DR FunFam; 3.50.50.60:FF:000233; Trypanothione reductase; 1. DR Gene3D; 3.30.390.30; -; 1. DR Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 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; IPR046952; GSHR/TRXR-like. 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 NCBIfam; TIGR01423; trypano_reduc; 1. DR PANTHER; PTHR42737; GLUTATHIONE REDUCTASE; 1. DR PANTHER; PTHR42737:SF2; GLUTATHIONE REDUCTASE; 1. DR Pfam; PF07992; Pyr_redox_2; 1. DR Pfam; PF02852; Pyr_redox_dim; 1. DR PIRSF; PIRSF000350; Mercury_reductase_MerA; 1. DR PRINTS; PR00368; FADPNR. DR PRINTS; PR00411; PNDRDTASEI. DR PRINTS; PR00470; TRYPANRDTASE. DR SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 1. DR SUPFAM; SSF55424; FAD/NAD-linked reductases, dimerisation (C-terminal) domain; 1. DR SUPFAM; SSF51971; Nucleotide-binding domain; 1. DR PROSITE; PS00076; PYRIDINE_REDOX_1; 1. DR PDBsum; 1AOG; -. DR PDBsum; 1BZL; -. DR PDBsum; 1GXF; -. DR PDBsum; 1NDA; -. 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 166..168 FT /evidence="ECO:0007829|PDB:1GXF" 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..422 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 458..460 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 //