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PDBsum entry 3n3s

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
3n3s
Jmol
Contents
Protein chains
714 a.a. *
Ligands
HEM ×2
MRD
MPD
Metals
_NA ×2
_CL ×3
Waters ×1509
* Residue conservation analysis
PDB id:
3n3s
Name: Oxidoreductase
Title: Crystal structure of the e198a variant of burkholderia pseud catalase-peroxidase katg with inh
Structure: Catalase-peroxidase. Chain: a, b. Engineered: yes. Mutation: yes
Source: Burkholderia pseudomallei. Organism_taxid: 28450. Gene: katg. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.70Å     R-factor:   0.154     R-free:   0.184
Authors: P.C.Loewen,B.Wiseman,X.Carpena,I.Fita
Key ref: B.Wiseman et al. (2010). Isonicotinic acid hydrazide conversion to Isonicotinyl-NAD by catalase-peroxidases. J Biol Chem, 285, 26662-26673. PubMed id: 20554537 DOI: 10.1074/jbc.M110.139428
Date:
20-May-10     Release date:   16-Jun-10    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
C6TXM5  (C6TXM5_BURPE) -  Catalase-peroxidase
Seq:
Struc:
 
Seq:
Struc:
728 a.a.
714 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.1.11.1.21  - Catalase peroxidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. Donor + H2O2 = oxidized donor + 2 H2O
2. 2 H2O2 = O2 + 2 H2O
Donor
+ H(2)O(2)
= oxidized donor
+ 2 × H(2)O
2 × H(2)O(2)
= O(2)
+ 2 × H(2)O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   3 terms 
  Biochemical function     nucleotide binding     6 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M110.139428 J Biol Chem 285:26662-26673 (2010)
PubMed id: 20554537  
 
 
Isonicotinic acid hydrazide conversion to Isonicotinyl-NAD by catalase-peroxidases.
B.Wiseman, X.Carpena, M.Feliz, L.J.Donald, M.Pons, I.Fita, P.C.Loewen.
 
  ABSTRACT  
 
Activation of the pro-drug isoniazid (INH) as an anti-tubercular drug in Mycobacterium tuberculosis involves its conversion to isonicotinyl-NAD, a reaction that requires the catalase-peroxidase, KatG. This report shows that the reaction proceeds in the absence of KatG at a slow rate in a mixture of INH, NAD+, Mn++ and O2, and that the inclusion of KatG increases the rate by >7 times. Superoxide, generated by either Mn++- or KatG-catalyzed reduction of O2, is an essential intermediate in the reaction. Elimination of the peroxidatic process by mutation, slows the rate of reaction by 60 % revealing that the peroxidatic process enhances, but is not essential for isonicotinyl-NAD formation. The isonicotinyl-NADo+ radical is identified as a reaction intermediate, and its reduction by superoxide is proposed. Binding sites for INH and its co-substrate, NAD+, are identified for the first time in crystal complexes of Burkholderia pseudomallei catalase-peroxidase with INH and NAD+ grown by co-crystallization. The best defined INH binding sites were identified, one in each subunit, on the opposite side of the protein from the entrance channel in a funnel shaped channel. The NAD+ binding site is about 20 Angstroms from the entrance to the heme cavity and involves interactions primarily with the AMP portion of the molecule in agreement with the NMR saturation transfer difference (STD) results.