TYTR_CRIFA
ID TYTR_CRIFA Reviewed; 491 AA.
AC P39040;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 137.
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 Crithidia fasciculata.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Crithidia.
OX NCBI_TaxID=5656;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1453951; DOI=10.1111/j.1365-2958.1992.tb01766.x;
RA Aboagye-Kwarteng T., Smith K., Fairlamb A.H.;
RT "Molecular characterization of the trypanothione reductase gene from
RT Crithidia fasciculata and Trypanosoma brucei: comparison with other
RT flavoprotein disulphide oxidoreductases with respect to substrate
RT specificity and catalytic mechanism.";
RL Mol. Microbiol. 6:3089-3099(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=1542316; DOI=10.1016/0166-6851(92)90243-d;
RA Field H., Cerami A., Henderson G.B.;
RT "Cloning, sequencing, and demonstration of polymorphism in trypanothione
RT reductase from Crithidia fasciculata.";
RL Mol. Biochem. Parasitol. 50:47-56(1992).
RN [3]
RP PROTEIN SEQUENCE OF 39-62, AND CHARACTERIZATION.
RX PubMed=3718941; DOI=10.1021/bi00360a007;
RA Shames S.L., Fairlamb A.H., Cerami A., Walsh C.T.;
RT "Purification and characterization of trypanothione reductase from
RT Crithidia fasciculata, a newly discovered member of the family of
RT disulfide-containing flavoprotein reductases.";
RL Biochemistry 25:3519-3526(1986).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), AND DISULFIDE BOND.
RX PubMed=8477734; DOI=10.1111/j.1432-1033.1993.tb17734.x;
RA Bailey S., Smith K., Fairlamb A.H., Hunter W.N.;
RT "Substrate interactions between trypanothione reductase and N1-
RT glutathionylspermidine disulphide at 0.28-nm resolution.";
RL Eur. J. Biochem. 213:67-75(1993).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=1522596; DOI=10.1016/0022-2836(92)90701-k;
RA Hunter W.N., Bailey S., Habash J., Harrop S.J., Helliwell J.R.,
RA Aboagye-Kwarteng T., Smith K., Fairlamb A.H.;
RT "Active site of trypanothione reductase. A target for rational drug
RT design.";
RL J. Mol. Biol. 227:322-333(1992).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=15299452; DOI=10.1107/s0907444993011898;
RA Bailey S., Fairlamb A.H., Hunter W.N.;
RT "Structure of trypanothione reductase from Crithidia fasciculata at 2.6-A
RT resolution; enzyme-NADP interactions at 2.8-A resolution.";
RL Acta Crystallogr. D 50:139-154(1994).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS).
RX PubMed=15299300; DOI=10.1107/s0907444994010772;
RA Strickland C.L., Puchalski R., Savvides S.N., Karplus P.A.;
RT "Overexpression of Crithidia fasciculata trypanothione reductase and
RT crystallization using a novel geometry.";
RL Acta Crystallogr. D 51:337-341(1995).
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5-8.0.;
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- PTM: The N-terminus is blocked.
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; Z12618; CAA78264.1; -; Genomic_DNA.
DR EMBL; M73323; AAA30321.1; -; mRNA.
DR EMBL; M73324; AAA30322.1; -; Genomic_DNA.
DR EMBL; M73325; AAA30323.1; -; Genomic_DNA.
DR PIR; S28002; S28002.
DR PDB; 1FEA; X-ray; 2.20 A; A/B/C/D=2-491.
DR PDB; 1FEB; X-ray; 2.00 A; A/B=2-491.
DR PDB; 1FEC; X-ray; 1.70 A; A/B=2-491.
DR PDB; 1TYP; X-ray; 2.80 A; A/B=1-487.
DR PDB; 1TYT; X-ray; 2.60 A; A/B=1-487.
DR PDB; 2TPR; X-ray; 2.40 A; A/B=2-491.
DR PDBsum; 1FEA; -.
DR PDBsum; 1FEB; -.
DR PDBsum; 1FEC; -.
DR PDBsum; 1TYP; -.
DR PDBsum; 1TYT; -.
DR PDBsum; 2TPR; -.
DR AlphaFoldDB; P39040; -.
DR SMR; P39040; -.
DR BindingDB; P39040; -.
DR ChEMBL; CHEMBL5394; -.
DR KEGG; ag:CAA78264; -.
DR VEuPathDB; TriTrypDB:CFAC1_020010000; -.
DR BioCyc; MetaCyc:MON-13293; -.
DR EvolutionaryTrace; P39040; -.
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; Direct protein sequencing; Disulfide bond; FAD;
KW Flavoprotein; NADP; Oxidoreductase; Redox-active center.
FT CHAIN 1..491
FT /note="Trypanothione reductase"
FT /id="PRO_0000067988"
FT ACT_SITE 461
FT /note="Proton acceptor"
FT BINDING 35..51
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT DISULFID 52..57
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:8477734"
FT VARIANT 479
FT /note="Q -> E"
FT CONFLICT 16
FT /note="G -> R (in Ref. 2; AAA30322/AAA30323)"
FT /evidence="ECO:0000305"
FT CONFLICT 62
FT /note="L -> Y (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 297
FT /note="D -> E (in Ref. 2; AAA30321/AAA30322/AAA30323)"
FT /evidence="ECO:0000305"
FT CONFLICT 454
FT /note="F -> V (in Ref. 2; AAA30322/AAA30323)"
FT /evidence="ECO:0000305"
FT STRAND 4..10
FT /evidence="ECO:0007829|PDB:1FEC"
FT HELIX 14..27
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 31..36
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 38..41
FT /evidence="ECO:0007829|PDB:1FEC"
FT TURN 42..44
FT /evidence="ECO:0007829|PDB:1FEC"
FT HELIX 51..55
FT /evidence="ECO:0007829|PDB:1FEC"
FT HELIX 57..75
FT /evidence="ECO:0007829|PDB:1FEC"
FT HELIX 76..79
FT /evidence="ECO:0007829|PDB:1FEC"
FT HELIX 85..87
FT /evidence="ECO:0007829|PDB:1FEC"
FT HELIX 92..115
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 120..131
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 134..142
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 147..158
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:1FEC"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:1FEC"
FT HELIX 178..181
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 189..194
FT /evidence="ECO:0007829|PDB:1FEC"
FT HELIX 198..210
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 216..227
FT /evidence="ECO:0007829|PDB:1FEC"
FT HELIX 232..244
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 247..251
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 255..260
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 266..270
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 275..283
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 287..290
FT /evidence="ECO:0007829|PDB:1FEC"
FT HELIX 292..294
FT /evidence="ECO:0007829|PDB:1FEA"
FT HELIX 296..299
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 322..324
FT /evidence="ECO:0007829|PDB:1FEC"
FT HELIX 326..329
FT /evidence="ECO:0007829|PDB:1FEC"
FT HELIX 335..350
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 364..366
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 368..370
FT /evidence="ECO:0007829|PDB:1TYT"
FT STRAND 372..376
FT /evidence="ECO:0007829|PDB:1FEC"
FT HELIX 379..385
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 387..396
FT /evidence="ECO:0007829|PDB:1FEC"
FT HELIX 399..404
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 411..418
FT /evidence="ECO:0007829|PDB:1FEC"
FT TURN 419..421
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 423..431
FT /evidence="ECO:0007829|PDB:1FEC"
FT HELIX 434..446
FT /evidence="ECO:0007829|PDB:1FEC"
FT HELIX 451..455
FT /evidence="ECO:0007829|PDB:1FEC"
FT HELIX 465..469
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 475..479
FT /evidence="ECO:0007829|PDB:1FEC"
FT STRAND 482..484
FT /evidence="ECO:0007829|PDB:1FEC"
SQ SEQUENCE 491 AA; 53229 MW; EF749215A16F9187 CRC64;
MSRAYDLVVI GAGSGGLEAG WNAASLHKKR VAVIDLQKHH GPPHYAALGG TCVNVGCVPK
KLMVTGANYM DTIRESAGFG WELDRESVRP NWKALIAAKN KAVSGINDSY EGMFADTEGL
TFHQGFGALQ DNHTVLVRES ADPNSAVLET LDTEYILLAT GSWPQHLGIE GDDLCITSNE
AFYLDEAPKR ALCVGGGYIS IEFAGIFNAY KARGGQVDLA YRGDMILRGF DSELRKQLTE
QLRANGINVR THENPAKVTK NADGTRHVVF ESGAEADYDV VMLAIGRVPR SQTLQLDKAG
VEVAKNGAIK VDAYSKTNVD NIYAIGDVTD RVMLTPVAIN EGAAFVDTVF ANKPRATDHT
KVACAVFSIP PMGVCGYVEE DAAKKYDQVA VYESSFTPLM HNISGSTYKK FMVRIVTNHA
DGEVLGVHML GDSSPEIIQS VAICLKMGAK ISDFYNTIGV HPTSAEELCS MRTPAYFYQK
GKRVEKIDSN L
