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

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 ox...

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Bibliographic Details
Published in:	Nature structural biology Vol. 6; no. 2; pp. 182 - 190
Main Authors:	Charon, Marie-Helene, Volbeda, Anne, Chabrière, Eric, Pieulle, Laetitia, Hatchikian, Etienne Claude, Fontecilla-Camps, Juan-Carlos
Format:	Journal Article
Language:	English
Published:	United States 01-02-1999
Subjects:	Binding Sites Catalysis Crystallography, X-Ray Desulfovibrio africanus Electrons Enzyme Activation Ketone Oxidoreductases - chemistry Ketone Oxidoreductases - metabolism Models, Molecular Oxygen - chemistry Protein Conformation Pyruvate Synthase Pyruvic Acid - chemistry
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	1072-8368 2331-365X
DOI:	10.1038/5870