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PDBsum entry 1aog
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Oxidoreductase PDB id
1aog

 

 

 

 

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Contents
Protein chains
485 a.a. *
Ligands
FAD ×2
MAE ×2
Waters ×419
* Residue conservation analysis
PDB id:
1aog
Name: Oxidoreductase
Title: Trypanosoma cruzi trypanothione reductase (oxidized form)
Structure: Trypanothione reductase. Chain: a, b. Ec: 1.6.4.8
Source: Trypanosoma cruzi. Organism_taxid: 5693. Strain: brazilian silvio strain clone x10/1
Biol. unit: Homo-Dimer (from PDB file)
Resolution:
2.30Å     R-factor:   0.189    
Authors: C.S.Bond,Y.Zhang,W.N.Hunter
Key ref:
Y.Zhang et al. (1996). The crystal structure of trypanothione reductase from the human pathogen Trypanosoma cruzi at 2.3 A resolution. Protein Sci, 5, 52-61. PubMed id: 8771196 DOI: 10.1002/pro.5560050107
Date:
03-Jul-97     Release date:   17-Sep-97    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P28593  (TYTR_TRYCR) -  Trypanothione reductase from Trypanosoma cruzi
Seq:
Struc: 		492 a.a.
485 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 7 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.1.8.1.12  - trypanothione-disulfide reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: trypanothione + NADP+ = trypanothione disulfide + NADPH + H+
trypanothione
 + NADP(+)
 = trypanothione disulfide
 + NADPH
 + H(+)
      Cofactor: FAD
FAD
Bound ligand (Het Group name = FAD) corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1002/pro.5560050107 Protein Sci 5:52-61 (1996)
PubMed id: 8771196  
 
 
The crystal structure of trypanothione reductase from the human pathogen Trypanosoma cruzi at 2.3 A resolution.
Y.Zhang, C.S.Bond, S.Bailey, M.L.Cunningham, A.H.Fairlamb, W.N.Hunter.
 
  ABSTRACT  
 
Trypanothione reductase (TR) is an NADPH-dependent flavoprotein unique to protozoan parasites from the genera Trypanosoma and Leishmania and is an important target for the design of improved trypanocidal drugs. We present details of the structure of TR from the human pathogen Trypanosoma cruzi, the agent responsible for Chagas' disease or South American trypanosomiasis. The structure has been solved by molecular replacement, using as the starting model the structure of the enzyme from the nonpathogenic Crithidia fasciculata, and refined to an R-factor of 18.9% for 53,868 reflections with F > or = sigma F between 8.0 and 2.3 A resolution. The model comprises two subunits (968 residues), two FAD prosthetic groups, two maleate ions, and 419 water molecules. The accuracy and geometry of the enzyme model is improved with respect to the C. fasciculata enzyme model. The new structure is described and specific features of the enzyme involved in substrate interactions are compared with previous models of TR and related glutathione reductases from human and Escherichia coli. Structural differences at the edge of the active sites suggest an explanation for the differing specificities toward glutathionylspermidine disulfide.
 
  Selected figure(s)  
 
Figure 7.
Fig. 7. Distribution of chrgeinandaroundthe disulfide bindingsites of (A) T. cruzi TR; (B) human GR; and (C) E. oli GR. Figurespro- ducedwith (Nicholls, 1993) and coloredas follows: white,neu- tral; red, negative harge; blue, positive charges. Coordinates for GR structureswereretrievd from the Brookhaven Protein Data Bank. 		Figure 10.
Fig. 10. Stereo view t show thetriad Glu-His-Water system in active site Athat may protonation of th active site base His 461. Blue dashed lines represent hydrogen bonds.Atoms are colored as follows: N, cyan; 0, red; C, grey.
 
  The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (1996, 5, 52-61) copyright 1996.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19747949 D.C.Jones, A.Ariza, W.H.Chow, S.L.Oza, and A.H.Fairlamb (2010).
Comparative structural, kinetic and inhibitor studies of Trypanosoma brucei trypanothione reductase with T. cruzi.
  Mol Biochem Parasitol, 169, 12-19.
PDB codes: 2ve2 2wba
20045436 P.K.Fyfe, M.S.Alphey, and W.N.Hunter (2010).
Structure of Trypanosoma brucei glutathione synthetase: domain and loop alterations in the catalytic cycle of a highly conserved enzyme.
  Mol Biochem Parasitol, 170, 93-99.
PDB code: 2wyo
19886864 S.Patel, S.Hussain, R.Harris, S.Sardiwal, J.M.Kelly, S.R.Wilkinson, P.C.Driscoll, and S.Djordjevic (2010).
Structural insights into the catalytic mechanism of Trypanosoma cruzi GPXI (glutathione peroxidase-like enzyme I).
  Biochem J, 425, 513-522.
PDB code: 3e0u
19924760 D.Spinks, E.J.Shanks, L.A.Cleghorn, S.McElroy, D.Jones, D.James, A.H.Fairlamb, J.A.Frearson, P.G.Wyatt, and I.H.Gilbert (2009).
Investigation of trypanothione reductase as a drug target in Trypanosoma brucei.
  ChemMedChem, 4, 2060-2069.  
19364854 G.A.Holloway, W.N.Charman, A.H.Fairlamb, R.Brun, M.Kaiser, E.Kostewicz, P.M.Novello, J.P.Parisot, J.Richardson, I.P.Street, K.G.Watson, and J.B.Baell (2009).
Trypanothione reductase high-throughput screening campaign identifies novel classes of inhibitors with antiparasitic activity.
  Antimicrob Agents Chemother, 53, 2824-2833.  
19296695 R.Perez-Pineiro, A.Burgos, D.C.Jones, L.C.Andrew, H.Rodriguez, M.Suarez, A.H.Fairlamb, and D.S.Wishart (2009).
Development of a novel virtual screening cascade protocol to identify potential trypanothione reductase inhibitors.
  J Med Chem, 52, 1670-1680.  
19557802 S.Patterson, D.C.Jones, E.J.Shanks, J.A.Frearson, I.H.Gilbert, P.G.Wyatt, and A.H.Fairlamb (2009).
Synthesis and evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) analogues as inhibitors of trypanothione reductase.
  ChemMedChem, 4, 1341-1353.  
18060667 D.B.Castro-Pinto, M.Genestra, G.B.Menezes, M.Waghabi, A.Gonçalves, C.De Nigris Del Cistia, C.M.Sant'Anna, L.L.Leon, and L.Mendonça-Lima (2008).
Cloning and expression of trypanothione reductase from a New World Leishmania species.
  Arch Microbiol, 189, 375-384.  
17582174 T.N.Gustafsson, T.Sandalova, J.Lu, A.Holmgren, and G.Schneider (2007).
High-resolution structures of oxidized and reduced thioredoxin reductase from Helicobacter pylori.
  Acta Crystallogr D Biol Crystallogr, 63, 833-843.
PDB codes: 2q0k 2q0l
  17012768 T.Jaeger, and L.Flohé (2006).
The thiol-based redox networks of pathogens: unexploited targets in the search for new drugs.
  Biofactors, 27, 109-120.  
16217027 E.I.Biterova, A.A.Turanov, V.N.Gladyshev, and J.J.Barycki (2005).
Crystal structures of oxidized and reduced mitochondrial thioredoxin reductase provide molecular details of the reaction mechanism.
  Proc Natl Acad Sci U S A, 102, 15018-15023.
PDB codes: 1zdl 1zkq
12033427 B.Hofmann, H.J.Hecht, and L.Flohé (2002).
Peroxiredoxins.
  Biol Chem, 383, 347-364.  
9545063 P.A.van den Berg, A.van Hoek, C.D.Walentas, R.N.Perham, and A.J.Visser (1998).
Flavin fluorescence dynamics and photoinduced electron transfer in Escherichia coli glutathione reductase.
  Biophys J, 74, 2046-2058.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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