Crystal structures of the key anaerobic enzyme pyruvate:ferredoxin oxidoreductase, free and in complex with pyruvate
Eric Chabrière1, Marie−Helene Charon1, Anne Volbeda1, Laetitia Pieulle2, Etienne Claude Hatchikian2
& Juan−Carlos Fontecilla−Camps1
1
Laboratoire de Cristallographie et de Cristallogénèse des Protéines, Institut de Biologie Structurale J.−P. Ebel CEA−CNRS, 41 avenue des Martyrs, 38027 Grenoble, France.
2
Unité de Bioénergétique et Ingénierie des Protéines, Institut de Biologie Structurale et Microbiologie CNRS, 31 chemin J. Aiguier,
13402 Marseille, France.
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 Å resolution), and of its complex with pyruvate (3.0 Å 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.
