P28593 (TYTR_TRYCR) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Trypanothione reductase
Short name=TR
EC=1.8.1.12

Alternative name(s):
N(1),N(8)-bis(glutathionyl)spermidine reductase

Gene names

Name:

TPR

Organism

Trypanosoma cruzi

Taxonomic identifier

5693 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Euglenozoa › Kinetoplastida › Trypanosomatidae › Trypanosoma › Schizotrypanum

Protein attributes

Sequence length	492 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Trypanothione is the parasite analog of glutathione; this enzyme is the equivalent of glutathione reductase.
Catalytic activity	Trypanothione + NADP+ = trypanothione disulfide + NADPH.
Cofactor	Binds 1 FAD per subunit.
Subunit structure	Homodimer.
Subcellular location	Cytoplasm.
Miscellaneous	The active site is a redox-active disulfide bond.
Sequence similarities	Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.

Ontologies

Keywords
Cellular component	Cytoplasm
Domain	Redox-active center
Ligand	FAD Flavoprotein NADP
Molecular function	Oxidoreductase
PTM	Disulfide bond
Technical term	3D-structure
Gene Ontology (GO)
Biological_process	cell redox homeostasis Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	disulfide oxidoreductase activity Inferred from electronic annotation. Source: InterPro flavin adenine dinucleotide binding Inferred from electronic annotation. Source: InterPro trypanothione-disulfide reductase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 492

492

Trypanothione reductase

PRO_0000067992

Regions

Nucleotide binding

36 – 52

17

FAD

Sites

Active site

461

1

Proton acceptor By similarity

Amino acid modifications

Disulfide bond

53 ↔ 58

Redox-active Ref.3

Natural variations

Natural variant

95

1

K → N in strain: Silvio.

Natural variant

140

1

E → A in strain: Silvio.

Natural variant

156

1

N → H in strain: Silvio.

Natural variant

353

1

N → T in strain: Silvio.

Natural variant

402 – 403

2

NI → KV in strain: Silvio.

Natural variant

441

1

V → I in strain: Silvio.

Secondary structure

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492

Helix Strand Turn

Details...

Beta strand

5 – 11

7

Helix

15 – 26

12

Beta strand

32 – 37

6

Beta strand

39 – 42

4

Turn

43 – 45

3

Helix

51 – 56

6

Helix

58 – 76

19

Helix

77 – 80

4

Helix

86 – 88

3

Helix

93 – 117

25

Beta strand

121 – 132

12

Beta strand

135 – 143

9

Beta strand

148 – 155

8

Beta strand

157 – 159

3

Beta strand

163 – 165

3

Helix

173 – 175

3

Helix

179 – 182

4

Beta strand

190 – 195

6

Helix

199 – 211

13

Beta strand

217 – 228

12

Helix

233 – 245

13

Beta strand

249 – 253

5

Beta strand

256 – 261

6

Beta strand

267 – 271

5

Beta strand

276 – 284

9

Beta strand

288 – 290

3

Helix

293 – 295

3

Helix

297 – 299

3

Beta strand

306 – 309

4

Beta strand

322 – 324

3

Helix

326 – 329

4

Helix

335 – 350

16

Beta strand

351 – 353

3

Beta strand

364 – 366

3

Beta strand

372 – 376

5

Helix

379 – 385

7

Beta strand

387 – 396

10

Helix

399 – 404

6

Beta strand

411 – 418

8

Turn

419 – 421

3

Beta strand

423 – 431

9

Helix

434 – 446

13

Helix

451 – 455

5

Helix

465 – 469

5

Beta strand

475 – 479

5

Beta strand

482 – 484

3

Sequences

	Sequence		Length	Mass (Da)
	P28593 [UniParc]. Last modified December 1, 1992. Version 1. Checksum: 4AF179952A20750F	FASTA	492	53,868
	10 20 30 40 50 60 MMSKIFDLVV IGAGSGGLEA AWNAATLYKK RVAVIDVQMV HGPPFFSALG GTCVNVGCVP 70 80 90 100 110 120 KKLMVTGAQY MEHLRESAGF GWEFDRTTLR AEWKKLIAVK DEAVLNINKS YEEMFRDTEG 130 140 150 160 170 180 LEFFLGWGSL ESKNVVNVRE SADPASAVKE RLETENILLA SGSWPHMPNI PGIEHCISSN 190 200 210 220 230 240 EAFYLPEPPR RVLTVGGGFI SVEFAGIFNA YKPKDGQVTL CYRGEMILRG FDHTLREELT 250 260 270 280 290 300 KQLTANGIQI LTKENPAKVE LNADGSKSVT FESGKKMDFD LVMMAIGRSP RTKDLQLQNA 310 320 330 340 350 360 GVMIKNGGVQ VDEYSRTNVS NIYAIGDVTN RVMLTPVAIN EAAALVDTVF GTNPRKTDHT 370 380 390 400 410 420 RVASAVFSIP PIGTCGLIEE VASKRYEVVA VYLSSFTPLM HNISGSKYKT FVAKIITNHS 430 440 450 460 470 480 DGTVLGVHLL GDNAPEIIQG VGICLKLNAK ISDFYNTIGV HPTSAEELCS MRTPSYYYVK 490 GEKMEKPSEA SL

References

[1]	"Cloning, sequencing, overproduction and purification of trypanothione reductase from Trypanosoma cruzi." Sullivan F.X., Walsh C.T. Mol. Biochem. Parasitol. 44:145-148(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Site-directed mutagenesis of the redox-active cysteines of Trypanosoma cruzi trypanothione reductase." Borges A., Cunningham M.L., Tover J., Fairlamb A.H. Eur. J. Biochem. 228:745-752(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Silvio.
[3]	"Crystallization and preliminary crystallographic analysis of trypanothione reductase from Trypanosoma cruzi, the causative agent of Chagas' disease." Krauth-Siegel R.L., Sticherling C., Jost I., Walsh C.T., Pai E.F., Kabsch W., Lantwin C.B. FEBS Lett. 317:105-108(1993) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 2-492, DISULFIDE BOND.
[4]	"The structure of Trypanosoma cruzi trypanothione reductase in the oxidized and NADPH reduced state." Lantwin C.B., Schlichting I., Kabsch W., Pai E.F., Krauth-Siegel R.L. Proteins 18:161-173(1994) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS).
[5]	"The crystal structure of trypanothione reductase from the human pathogen Trypanosoma cruzi at 2.3-A resolution." Zhang Y., Bond C.S., Bailey S., Cunningham M.L., Fairlamb A.H., Hunter W.N. Protein Sci. 5:52-61(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS). Strain: Silvio.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M38051 Genomic DNA. Translation: AAA63547.1.
Z13958 Genomic DNA. Translation: CAA78360.1.

PIR

S68968.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AOG	X-ray	2.30	A/B	3-487	[»]
1BZL	X-ray	2.40	A/B	2-487	[»]
1GXF	X-ray	2.70	A/B	1-492	[»]
1NDA	X-ray	3.30	A/B/C/D	2-492	[»]

ProteinModelPortal

P28593.

SMR

P28593. Positions 5-485.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

Gene3D

3.30.390.30. 1 hit.

InterPro

IPR016156. FAD/NAD-linked_Rdtase_dimer.
IPR013027. FAD_pyr_nucl-diS_OxRdtase.
IPR004099. Pyr_nucl-diS_OxRdtase_dimer.
IPR023753. Pyr_nucl-diS_OxRdtase_FAD/NAD.
IPR012999. Pyr_OxRdtase_I_AS.
IPR001327. Pyr_OxRdtase_NAD-bd_dom.
IPR001864. Trypnth_redctse.
[Graphical view]

Pfam

PF00070. Pyr_redox. 1 hit.
PF07992. Pyr_redox_2. 1 hit.
PF02852. Pyr_redox_dim. 1 hit.
[Graphical view]

PRINTS

PR00368. FADPNR.
PR00470. TRYPANRDTASE.

SUPFAM

SSF55424. FAD/NAD-linked_reductase_dimer. 1 hit.

TIGRFAMs

TIGR01423. trypano_reduc. 1 hit.

PROSITE

PS00076. PYRIDINE_REDOX_1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P28593.

ChEMBL

CHEMBL5131.

EvolutionaryTrace

P28593.

Entry information

Entry name

TYTR_TRYCR

Accession

Primary (citable) accession number: P28593

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	December 1, 1992
Last modified:	April 3, 2013
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)