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PDBsum entry 1w1c
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protein ligands Protein-protein interface(s) links
Electron transport PDB id
1w1c

 

 

 

 

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Contents
Protein chains
489 a.a.
105 a.a.
Ligands
FAD ×2
NDP ×2
Theoretical model
PDB id:
1w1c
Name: Electron transport
Title: Human cytoplasmic thioredoxin reductase (txn1) in complex with thioredoxin (trx)
Structure: Thioredoxin reductase. Synonym: tr, tr1. Chain: a, b. Other_details: homodimer contains NADP+fad/subunit. Thioredoxin. Synonym: atl-derived factor, adf, surface associated sulphydryl protein, sasp. Chain: c
Source: Homo sapiens. Human. Tissue: placenta, brain. Cellular_location: cytoplasm. Human
Authors: W.Brandt,L.A.Wessjohann
Key ref: W.Brandt and L.A.Wessjohann (2005). The functional role of selenocysteine (Sec) in the catalysis mechanism of large thioredoxin reductases: proposition of a swapping catalytic triad including a Sec-His-Glu state. Chembiochem, 6, 386-394. PubMed id: 15651042 DOI: 10.1002/cbic.200400276
Date:
21-Jun-04     Release date:   19-Jan-05    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q16881  (TRXR1_HUMAN) -  Thioredoxin reductase 1, cytoplasmic from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		649 a.a.
489 a.a.*
Protein chain
Pfam   ArchSchema ?
P10599  (THIO_HUMAN) -  Thioredoxin from Homo sapiens
Seq:
Struc: 		105 a.a.
105 a.a.
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.1.8.1.9  - thioredoxin-disulfide reductase (NADPH).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: [thioredoxin]-dithiol + NADP+ = [thioredoxin]-disulfide + NADPH + H+
[thioredoxin]-dithiol
 + NADP(+)
 = [thioredoxin]-disulfide
 + NADPH
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1002/cbic.200400276 Chembiochem 6:386-394 (2005)
PubMed id: 15651042  
 
 
The functional role of selenocysteine (Sec) in the catalysis mechanism of large thioredoxin reductases: proposition of a swapping catalytic triad including a Sec-His-Glu state.
W.Brandt, L.A.Wessjohann.
 
  ABSTRACT  
 
Thioredoxin reductases catalyse the reduction of thioredoxin disulfide and some other oxidised cell constituents. They are homodimeric proteins containing one FAD and accepting one NADPH per subunit as essential cofactors. Some of these reductases contain a selenocysteine at the C terminus. Based on the X-ray structure of rat thioredoxin reductase, homology models of human thioredoxin reductase were created and subsequently docked to thioredoxin to model the active complex. The formation of a new type of a catalytic triad between selenocysteine, histidine and a glutamate could be detected in the protein structure. By means of DFT (B3LYP, lacv3p**) calculations, we could show that the formation of such a triad is essential to support the proton transfer from selenol to a histidine to stabilise a selenolate anion, which is able to interact with the disulfide of thioredoxin and catalyses the reductive disulfide opening. Whereas a simple proton transfer from selenocysteine to histidine is thermodynamically disfavoured by some 18 kcal mol(-1), it becomes favoured when the carboxylic acid group of a glutamate stabilises the formed imidazole cation. An identical process with a cysteine instead of selenocysteine will require 4 kcal mol(-1) more energy, which corresponds to a calculated equilibrium shift of approximately 1000:1 or a 10(3) rate acceleration: a value close to the experimental one of about 10(2) times. These results give new insights into the catalytic mechanism of thioredoxin reductase and, for the first time, explain the advantage of the incorporation of a selenocysteine instead of a cysteine residue in a protein.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19366212 A.P.Lothrop, E.L.Ruggles, and R.J.Hondal (2009).
No selenium required: reactions catalyzed by mammalian thioredoxin reductase that are independent of a selenocysteine residue.
  Biochemistry, 48, 6213-6223.  
19054767 Q.Cheng, T.Sandalova, Y.Lindqvist, and E.S.Arnér (2009).
Crystal structure and catalysis of the selenoprotein thioredoxin reductase 1.
  J Biol Chem, 284, 3998-4008.
PDB codes: 3ean 3eao
19406205 R.J.Hondal (2009).
Using chemical approaches to study selenoproteins-focus on thioredoxin reductases.
  Biochim Biophys Acta, 1790, 1501-1512.  
18327317 B.K.Sarma, and G.Mugesh (2008).
Thiol cofactors for selenoenzymes and their synthetic mimics.
  Org Biomol Chem, 6, 965-974.  
18357547 L.A.Wessjohann, and A.Schneider (2008).
Synthesis of selenocysteine and its derivatives with an emphasis on selenenylsulfide (-Se-S-) formation.
  Chem Biodivers, 5, 375-388.  
18357559 M.Iwaoka, R.Ooka, T.Nakazato, S.Yoshida, and S.Oishi (2008).
Synthesis of selenocysteine and selenomethionine derivatives from sulfur-containing amino acids.
  Chem Biodivers, 5, 359-374.  
17937624 A.Schneider, W.Brandt, and L.A.Wessjohann (2007).
Influence of pH and flanking serine on the redox potential of S-S and S-Se bridges of Cys-Cys and Cys-Sec peptides.
  Biol Chem, 388, 1099-1101.  
17937613 L.A.Wessjohann, A.Schneider, M.Abbas, and W.Brandt (2007).
Selenium in chemistry and biochemistry in comparison to sulfur.
  Biol Chem, 388, 997.  
16432576 M.Abbas, J.Bethke, and L.A.Wessjohann (2006).
One pot synthesis of selenocysteine containing peptoid libraries by Ugi multicomponent reactions in water.
  Chem Commun (Camb), (), 541-543.  
16950793 P.J.McMillan, L.D.Arscott, D.P.Ballou, K.Becker, C.H.Williams, and S.Müller (2006).
Identification of acid-base catalytic residues of high-Mr thioredoxin reductase from Plasmodium falciparum.
  J Biol Chem, 281, 32967-32977.  
16977661 S.Gromer, L.A.Wessjohann, J.Eubel, and W.Brandt (2006).
Mutational studies confirm the catalytic triad in the human selenoenzyme thioredoxin reductase predicted by molecular modeling.
  Chembiochem, 7, 1649-1652.  
17056271 S.Urig, and K.Becker (2006).
On the potential of thioredoxin reductase inhibitors for cancer therapy.
  Semin Cancer Biol, 16, 452-465.  
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
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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