PDBsum entry 2c3p

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chains
1231 a.a. *
SF4 ×6
1TP ×2
_CA ×2
_MG ×2
Waters ×851
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of the free radical intermediate of pyruvate:ferredoxin oxidoreductase from desulfovibrio africanus
Structure: Pyruvate-ferredoxin oxidoreductase. Chain: a, b. Other_details: complexed with iron/sulfur cluster, thiamin diphosphate, crystal soaked 40 minutes with pyruvate
Source: Desulfovibrio africanus. Organism_taxid: 873
Biol. unit: Dimer (from PDB file)
2.33Å     R-factor:   0.171     R-free:   0.223
Authors: C.Cavazza,C.Contreras-Martel,L.Pieulle,E.Chabriere, E.C.Hatchikian,J.C.Fontecilla-Camps
Key ref:
C.Cavazza et al. (2006). Flexibility of thiamine diphosphate revealed by kinetic crystallographic studies of the reaction of pyruvate-ferredoxin oxidoreductase with pyruvate. Structure, 14, 217-224. PubMed id: 16472741 DOI: 10.1016/j.str.2005.10.013
11-Oct-05     Release date:   15-Feb-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P94692  (P94692_DESAF) -  Pyruvate-flavodoxin oxidoreductase
1232 a.a.
1231 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   3 terms 
  Biochemical function     catalytic activity     8 terms  


DOI no: 10.1016/j.str.2005.10.013 Structure 14:217-224 (2006)
PubMed id: 16472741  
Flexibility of thiamine diphosphate revealed by kinetic crystallographic studies of the reaction of pyruvate-ferredoxin oxidoreductase with pyruvate.
C.Cavazza, C.Contreras-Martel, L.Pieulle, E.Chabrière, E.C.Hatchikian, J.C.Fontecilla-Camps.
Pyruvate-ferredoxin oxidoreductases (PFOR) are unique among thiamine pyrophosphate (ThDP)-containing enzymes in giving rise to a rather stable cofactor-based free-radical species upon the decarboxylation of their first substrate, pyruvate. We have obtained snapshots of unreacted and partially reacted (probably as a tetrahedral intermediate) pyruvate-PFOR complexes at different time intervals. We conclude that pyruvate decarboxylation involves very limited substrate-to-product movements but a significant displacement of the thiazolium moiety of ThDP. In this respect, PFOR seems to differ substantially from other ThDP-containing enzymes, such as transketolase and pyruvate decarboxylase. In addition, exposure of PFOR to oxygen in the presence of pyruvate results in significant inhibition of catalytic activity, both in solution and in the crystals. Examination of the crystal structure of inhibited PFOR suggests that the loss of activity results from oxime formation at the 4' amino substituent of the pyrimidine moiety of ThDP.
  Selected figure(s)  
Figure 2.
Figure 2. Electron Density Map of Oxygen-Inhibited PFOR
Pyruvate was excluded from phase and structure factor calculations (omit map). The electron density peak next to N4' of the aminopyrimidine ring may represent the oxygen atom of an oxime moiety. This and the displacement of a water molecule are the only differences between inhibited and active PFORs (see Figure 3A). This figure and Figure 3 and Figure 6 were prepared with TURBO (Roussel and Cambillaud, 1989).
  The above figure is reprinted by permission from Cell Press: Structure (2006, 14, 217-224) copyright 2006.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19490097 K.Agyei-Owusu, and F.J.Leeper (2009).
Thiamin diphosphate in biological chemistry: analogues of thiamin diphosphate in studies of enzymes and riboswitches.
  FEBS J, 276, 2905-2916.  
18570438 G.S.Brandt, N.Nemeria, S.Chakraborty, M.J.McLeish, A.Yep, G.L.Kenyon, G.A.Petsko, F.Jordan, and D.Ringe (2008).
Probing the active center of benzaldehyde lyase with substitutions and the pseudosubstrate analogue benzoylphosphonic acid methyl ester.
  Biochemistry, 47, 7734-7743.
PDB code: 3d7k
18801467 S.W.Ragsdale, and E.Pierce (2008).
Acetogenesis and the Wood-Ljungdahl pathway of CO(2) fixation.
  Biochim Biophys Acta, 1784, 1873-1898.  
18004749 V.I.Bunik, and D.Degtyarev (2008).
Structure-function relationships in the 2-oxo acid dehydrogenase family: substrate-specific signatures and functional predictions for the 2-oxoglutarate dehydrogenase-like proteins.
  Proteins, 71, 874-890.  
17403671 M.Kriek, F.Martins, R.Leonardi, S.A.Fairhurst, D.J.Lowe, and P.L.Roach (2007).
Thiazole synthase from Escherichia coli: an investigation of the substrates and purified proteins required for activity in vitro.
  J Biol Chem, 282, 17413-17423.  
17158936 P.S.Hoffman, G.Sisson, M.A.Croxen, K.Welch, W.D.Harman, N.Cremades, and M.G.Morash (2007).
Antiparasitic drug nitazoxanide inhibits the pyruvate oxidoreductases of Helicobacter pylori, selected anaerobic bacteria and parasites, and Campylobacter jejuni.
  Antimicrob Agents Chemother, 51, 868-876.  
16752902 S.O.Mansoorabadi, J.Seravalli, C.Furdui, V.Krymov, G.J.Gerfen, T.P.Begley, J.Melnick, S.W.Ragsdale, and G.H.Reed (2006).
EPR spectroscopic and computational characterization of the hydroxyethylidene-thiamine pyrophosphate radical intermediate of pyruvate:ferredoxin oxidoreductase.
  Biochemistry, 45, 7122-7131.  
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 code is shown on the right.