Article

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

Laboratoire de Cristallographie et de Cristallogénèse des Protéines, Institut de Biologie Structurale J.-P. Ebel CEA-CNRS, Grenoble, France.
Nature Structural Biology 03/1999; 6(2):182-90. DOI: 10.1038/5870
Source: PubMed

ABSTRACT 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.

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