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PDBsum entry 4dvh

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protein metals Protein-protein interface(s) links
Oxidoreductase PDB id
4dvh
Jmol
Contents
Protein chains
203 a.a.
Metals
_FE ×2
Waters ×102
PDB id:
4dvh
Name: Oxidoreductase
Title: Crystal structure of trypanosoma cruzi mitochondrial iron su dismutase
Structure: Superoxide dismutase. Chain: a, b. Engineered: yes
Source: Trypanosoma cruzi. Organism_taxid: 353153. Strain: cl brener. Gene: tc00.1047053509775.40. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.23Å     R-factor:   0.172     R-free:   0.220
Authors: N.Larrieux,A.Buschiazzo
Key ref: A.Martinez et al. (2014). Structural and molecular basis of the peroxynitrite-mediated nitration and inactivation of Trypanosoma cruzi iron-superoxide dismutases (Fe-SODs) A and B: disparate susceptibilities due to the repair of Tyr35 radical by Cys83 in Fe-SODB through intramolecular electron transfer. J Biol Chem, 289, 12760-12778. PubMed id: 24616096 DOI: 10.1074/jbc.M113.545590
Date:
23-Feb-12     Release date:   27-Mar-13    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q4DCQ3  (Q4DCQ3_TRYCC) -  Superoxide dismutase
Seq:
Struc:
233 a.a.
203 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.1.15.1.1  - Superoxide dismutase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 2 superoxide + 2 H+ = O2 + H2O2
2 × superoxide
+ 2 × H(+)
= O(2)
+ H(2)O(2)
      Cofactor: Fe cation or Mn(2+) or (Zn(2+) and Cu cation)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   2 terms 
  Biochemical function     superoxide dismutase activity     2 terms  

 

 
    Added reference    
 
 
DOI no: 10.1074/jbc.M113.545590 J Biol Chem 289:12760-12778 (2014)
PubMed id: 24616096  
 
 
Structural and molecular basis of the peroxynitrite-mediated nitration and inactivation of Trypanosoma cruzi iron-superoxide dismutases (Fe-SODs) A and B: disparate susceptibilities due to the repair of Tyr35 radical by Cys83 in Fe-SODB through intramolecular electron transfer.
A.Martinez, G.Peluffo, A.A.Petruk, M.Hugo, D.Piñeyro, V.Demicheli, D.M.Moreno, A.Lima, C.Batthyány, R.Durán, C.Robello, M.A.Martí, N.Larrieux, A.Buschiazzo, M.Trujillo, R.Radi, L.Piacenza.
 
  ABSTRACT  
 
Trypanosoma cruzi, the causative agent of Chagas disease, contains exclusively iron-dependent superoxide dismutases (Fe-SODs) located in different subcellular compartments. Peroxynitrite, a key cytotoxic and oxidizing effector biomolecule, reacted with T. cruzi mitochondrial (Fe-SODA) and cytosolic (Fe-SODB) SODs with second order rate constants of 4.6 ± 0.2 × 10(4) m(-1) s(-1) and 4.3 ± 0.4 × 10(4) m(-1) s(-1) at pH 7.4 and 37 °C, respectively. Both isoforms are dose-dependently nitrated and inactivated by peroxynitrite. Susceptibility of T. cruzi Fe-SODA toward peroxynitrite was similar to that reported previously for Escherichia coli Mn- and Fe-SODs and mammalian Mn-SOD, whereas Fe-SODB was exceptionally resistant to oxidant-mediated inactivation. We report mass spectrometry analysis indicating that peroxynitrite-mediated inactivation of T. cruzi Fe-SODs is due to the site-specific nitration of the critical and universally conserved Tyr(35). Searching for structural differences, the crystal structure of Fe-SODA was solved at 2.2 Å resolution. Structural analysis comparing both Fe-SOD isoforms reveals differences in key cysteines and tryptophan residues. Thiol alkylation of Fe-SODB cysteines made the enzyme more susceptible to peroxynitrite. In particular, Cys(83) mutation (C83S, absent in Fe-SODA) increased the Fe-SODB sensitivity toward peroxynitrite. Molecular dynamics, electron paramagnetic resonance, and immunospin trapping analysis revealed that Cys(83) present in Fe-SODB acts as an electron donor that repairs Tyr(35) radical via intramolecular electron transfer, preventing peroxynitrite-dependent nitration and consequent inactivation of Fe-SODB. Parasites exposed to exogenous or endogenous sources of peroxynitrite resulted in nitration and inactivation of Fe-SODA but not Fe-SODB, suggesting that these enzymes play distinctive biological roles during parasite infection of mammalian cells.