PDBsum entry 2pda

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chains
1231 a.a. *
SF4 ×6
TPP ×2
PYR ×2
_MG ×2
_CA ×2
Waters ×14
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of the complex between pyruvate-ferredoxin oxidoreductase from desulfovibrio africanus and pyruvate.
Structure: Protein (pyruvate-ferredoxin oxidoreductase). Chain: a, b. Other_details: complexed with iron/sulfur cluster, thiamin diphosphate, pyruvic acid
Source: Desulfovibrio africanus. Organism_taxid: 873. Strain: ncib 8401. Cellular_location: cytoplasm
Biol. unit: Dimer (from PQS)
3.00Å     R-factor:   0.234     R-free:   0.297
Authors: E.Chabriere,M.H.Charon
Key ref:
E.Chabrière et al. (1999). Crystal structures of the key anaerobic enzyme pyruvate:ferredoxin oxidoreductase, free and in complex with pyruvate. Nat Struct Biol, 6, 182-190. PubMed id: 10048931 DOI: 10.1038/5870
10-Nov-98     Release date:   23-Apr-99    
Go to PROCHECK summary

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

 Enzyme reactions 
   Enzyme class: E.C.  - Pyruvate synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Pyruvate + CoA + 2 oxidized ferredoxin = acetyl-CoA + CO2 + 2 reduced ferredoxin + 2 H+
+ CoA
+ 2 × oxidized ferredoxin
= acetyl-CoA
+ CO(2)
+ 2 × reduced ferredoxin
+ 2 × H(+)
      Cofactor: Iron-sulfur; Thiamine diphosphate
Thiamine diphosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     metabolic process   4 terms 
  Biochemical function     catalytic activity     9 terms  


DOI no: 10.1038/5870 Nat Struct Biol 6:182-190 (1999)
PubMed id: 10048931  
Crystal structures of the key anaerobic enzyme pyruvate:ferredoxin oxidoreductase, free and in complex with pyruvate.
E.Chabrière, M.H.Charon, A.Volbeda, L.Pieulle, E.C.Hatchikian, J.C.Fontecilla-Camps.
Oxidative decarboxylation of pyruvate to form acetyl-coenzyme A, a crucial step in many metabolic pathways, is carried out in most aerobic organisms by the multienzyme complex pyruvate dehydrogenase. In most anaerobes, the same reaction is usually catalyzed by a single enzyme, pyruvate:ferredoxin oxidoreductase (PFOR). Thus, PFOR is a potential target for drug design against certain anaerobic pathogens. Here, we report the crystal structures of the homodimeric Desulfovibrio africanus PFOR (data to 2.3 A resolution), and of its complex with pyruvate (3.0 A resolution). The structures show that each subunit consists of seven domains, one of which affords protection against oxygen. The thiamin pyrophosphate (TPP) cofactor and the three [4Fe-4S] clusters are suitably arranged to provide a plausible electron transfer pathway. In addition, the PFOR-pyruvate complex structure shows the noncovalent fixation of the substrate before the catalytic reaction.
  Selected figure(s)  
Figure 1.
Figure 1. Ribbon drawings of Desulfovibrio africanus PFOR, made with MOLSCRIPT^48 and Raster3D^49. a,b, Two perpendicular views. Subunits are shown in light blue and dark blue. TPP cofactors are highlighted in bright red, Mg ions in green, iron atoms in brown and sulfur atoms in yellow.
Figure 3.
Figure 3. Ribbon drawings of the seven structural domains of Desulfovibrio africanus PFOR. In the included topology diagrams, −helices are represented by circles and −strands by triangles. A common folding motif in the core domains I, II and VI is indicated by the dots in their topology diagrams. For clarity, domains and topology diagrams are not represented in the same orientation.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (1999, 6, 182-190) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20884694 P.Worm, A.J.Stams, X.Cheng, and C.M.Plugge (2011).
Growth- and substrate-dependent transcription of formate dehydrogenase and hydrogenase coding genes in Syntrophobacter fumaroxidans and Methanospirillum hungatei.
  Microbiology, 157, 280-289.  
20015072 T.Ikeda, M.Yamamoto, H.Arai, D.Ohmori, M.Ishii, and Y.Igarashi (2010).
Enzymatic and electron paramagnetic resonance studies of anabolic pyruvate synthesis by pyruvate: ferredoxin oxidoreductase from Hydrogenobacter thermophilus.
  FEBS J, 277, 501-510.  
19590008 A.S.Eustáquio, R.P.McGlinchey, Y.Liu, C.Hazzard, L.L.Beer, G.Florova, M.M.Alhamadsheh, A.Lechner, A.J.Kale, Y.Kobayashi, K.A.Reynolds, and B.S.Moore (2009).
Biosynthesis of the salinosporamide A polyketide synthase substrate chloroethylmalonyl-coenzyme A from S-adenosyl-L-methionine.
  Proc Natl Acad Sci U S A, 106, 12295-12300.  
19476486 B.Shaanan, and D.M.Chipman (2009).
Reaction mechanisms of thiamin diphosphate enzymes: new insights into the role of a conserved glutamate residue.
  FEBS J, 276, 2447-2453.  
19476487 K.Tittmann (2009).
Reaction mechanisms of thiamin diphosphate enzymes: redox reactions.
  FEBS J, 276, 2454-2468.  
18043855 S.J.Costelloe, J.M.Ward, and P.A.Dalby (2008).
Evolutionary Analysis of the TPP-Dependent Enzyme Family.
  J Mol Evol, 66, 36-49.  
18801467 S.W.Ragsdale, and E.Pierce (2008).
Acetogenesis and the Wood-Ljungdahl pathway of CO(2) fixation.
  Biochim Biophys Acta, 1784, 1873-1898.  
18378591 S.W.Ragsdale (2008).
Enzymology of the wood-Ljungdahl pathway of acetogenesis.
  Ann N Y Acad Sci, 1125, 129-136.  
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.  
17534532 A.W.Munro, H.M.Girvan, and K.J.McLean (2007).
Variations on a (t)heme--novel mechanisms, redox partners and catalytic functions in the cytochrome P450 superfamily.
  Nat Prod Rep, 24, 585-609.  
16430685 J.A.Imlay (2006).
Iron-sulphur clusters and the problem with oxygen.
  Mol Microbiol, 59, 1073-1082.  
16531404 P.Arjunan, M.Sax, A.Brunskill, K.Chandrasekhar, N.Nemeria, S.Zhang, F.Jordan, and W.Furey (2006).
A thiamin-bound, pre-decarboxylation reaction intermediate analogue in the pyruvate dehydrogenase E1 subunit induces large scale disorder-to-order transformations in the enzyme and reveals novel structural features in the covalently bound adduct.
  J Biol Chem, 281, 15296-15303.
PDB codes: 2g25 2g28
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.  
16603087 S.S.Krishna, R.I.Sadreyev, and N.V.Grishin (2006).
A tale of two ferredoxins: sequence similarity and structural differences.
  BMC Struct Biol, 6, 8.  
15752351 R.Golbik, L.E.Meshalkina, T.Sandalova, K.Tittmann, E.Fiedler, H.Neef, S.König, R.Kluger, G.A.Kochetov, G.Schneider, and G.Hübner (2005).
Effect of coenzyme modification on the structural and catalytic properties of wild-type transketolase and of the variant E418A from Saccharomyces cerevisiae.
  FEBS J, 272, 1326-1342.  
15305914 R.Rabus, A.Ruepp, T.Frickey, T.Rattei, B.Fartmann, M.Stark, M.Bauer, A.Zibat, T.Lombardot, I.Becker, J.Amann, K.Gellner, H.Teeling, W.D.Leuschner, F.O.Glöckner, A.N.Lupas, R.Amann, and H.P.Klenk (2004).
The genome of Desulfotalea psychrophila, a sulfate-reducing bacterium from permanently cold Arctic sediments.
  Environ Microbiol, 6, 887-902.  
14526024 C.Ebenau-Jehle, M.Boll, and G.Fuchs (2003).
2-Oxoglutarate:NADP(+) oxidoreductase in Azoarcus evansii: properties and function in electron transfer reactions in aromatic ring reduction.
  J Bacteriol, 185, 6119-6129.  
12594918 W.Martin, and M.J.Russell (2003).
On the origins of cells: a hypothesis for the evolutionary transitions from abiotic geochemistry to chemoautotrophic prokaryotes, and from prokaryotes to nucleated cells.
  Philos Trans R Soc Lond B Biol Sci, 358, 59.  
12146957 C.Furdui, and S.W.Ragsdale (2002).
The roles of coenzyme A in the pyruvate:ferredoxin oxidoreductase reaction mechanism: rate enhancement of electron transfer from a radical intermediate to an iron-sulfur cluster.
  Biochemistry, 41, 9921-9937.  
12081970 E.Dörner, and M.Boll (2002).
Properties of 2-oxoglutarate:ferredoxin oxidoreductase from Thauera aromatica and its role in enzymatic reduction of the aromatic ring.
  J Bacteriol, 184, 3975-3983.  
12142484 P.J.Keeling, and N.M.Fast (2002).
Microsporidia: biology and evolution of highly reduced intracellular parasites.
  Annu Rev Microbiol, 56, 93.  
12167658 T.Iwasaki, A.Kounosu, M.Aoshima, D.Ohmori, T.Imai, A.Urushiyama, N.J.Cosper, and R.A.Scott (2002).
Novel [2Fe-2S]-type redox center C in SdhC of archaeal respiratory complex II from Sulfolobus tokodaii strain 7.
  J Biol Chem, 277, 39642-39648.  
12475211 V.L.Davidson (2002).
Chemically gated electron transfer. A means of accelerating and regulating rates of biological electron transfer.
  Biochemistry, 41, 14633-14636.  
11422387 C.Y.Huang, A.K.Chang, P.F.Nixon, and R.G.Duggleby (2001).
Site-directed mutagenesis of the ionizable groups in the active site of Zymomonas mobilis pyruvate decarboxylase: effect on activity and pH dependence.
  Eur J Biochem, 268, 3558-3565.  
11179210 D.Dobritzsch, G.Schneider, K.D.Schnackerz, and Y.Lindqvist (2001).
Crystal structure of dihydropyrimidine dehydrogenase, a major determinant of the pharmacokinetics of the anti-cancer drug 5-fluorouracil.
  EMBO J, 20, 650-660.
PDB codes: 1h7w 1h7x
11752578 E.Chabrière, X.Vernède, B.Guigliarelli, M.H.Charon, E.C.Hatchikian, and J.C.Fontecilla-Camps (2001).
Crystal structure of the free radical intermediate of pyruvate:ferredoxin oxidoreductase.
  Science, 294, 2559-2563.
PDB code: 1kek
11683888 E.Fukuda, H.Kino, H.Matsuzawa, and T.Wakagi (2001).
Role of a highly conserved YPITP motif in 2-oxoacid:ferredoxin oxidoreductase: heterologous expression of the gene from Sulfolobus sp.strain 7, and characterization of the recombinant and variant enzymes.
  Eur J Biochem, 268, 5639-5646.  
11568186 K.S.Yoon, C.Bobst, C.F.Hemann, R.Hille, and F.R.Tabita (2001).
Spectroscopic and functional properties of novel 2[4Fe-4S] cluster-containing ferredoxins from the green sulfur bacterium Chlorobium tepidum.
  J Biol Chem, 276, 44027-44036.  
10745006 A.AEvarsson, J.L.Chuang, R.M.Wynn, S.Turley, D.T.Chuang, and W.G.Hol (2000).
Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease.
  Structure, 8, 277-291.
PDB code: 1dtw
10966480 R.N.Perham (2000).
Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions.
  Annu Rev Biochem, 69, 961.  
10848975 V.Bunik, A.H.Westphal, and Kok (2000).
Kinetic properties of the 2-oxoglutarate dehydrogenase complex from Azotobacter vinelandii evidence for the formation of a precatalytic complex with 2-oxoglutarate.
  Eur J Biochem, 267, 3583-3591.  
10491097 L.Pieulle, M.H.Charon, P.Bianco, J.Bonicel, Y.Pétillot, and E.C.Hatchikian (1999).
Structural and kinetic studies of the pyruvate-ferredoxin oxidoreductase/ferredoxin complex from Desulfovibrio africanus.
  Eur J Biochem, 264, 500-508.  
10607667 M.H.Charon, A.Volbeda, E.Chabriere, L.Pieulle, and J.C.Fontecilla-Camps (1999).
Structure and electron transfer mechanism of pyruvate:ferredoxin oxidoreductase.
  Curr Opin Struct Biol, 9, 663-669.  
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.