Crystal structures of the key anaerobic enzyme pyruvate:ferredoxin oxidoreductase, free and in complex with pyruvate

Nat Struct Biol. 1999 Feb;6(2):182-90. doi: 10.1038/5870.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Catalysis
  • Crystallography, X-Ray
  • Electrons
  • Enzyme Activation
  • Ketone Oxidoreductases / chemistry*
  • Ketone Oxidoreductases / metabolism
  • Models, Molecular
  • Oxygen / chemistry
  • Protein Conformation
  • Pyruvate Synthase
  • Pyruvic Acid / chemistry*


  • Pyruvic Acid
  • Ketone Oxidoreductases
  • Pyruvate Synthase
  • Oxygen

Associated data

  • PDB/1B0P
  • PDB/2PDA