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


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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    • "produce a second molecule of oxaloacetate, completing the network-autocatalytic topology and making the cycle selfamplifying . The distinctive reaction in the rTCA pathway is a carbonyl insertion at a thioester (acetyl-CoA or succinyl-CoA), performed by a family of conserved ferredoxin-dependent oxidoreductases which are triple-Fe 4 S 4 -cluster proteins [108]. "
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    Full-text · Article · Dec 2012 · Physical Biology
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    • "The X-ray crystal structure of the A 2 -type pyruvate:ferredoxin oxidoreductase from Desulfovibrio africanus has been determined byChabrì ere et al. [32] [33] and shown to contain one thiamine pyrophosphate, one Mg 2+ , and three [4Fe-4S] clusters as prosthetic groups per protomer . The ab-/a 2 b 2 -type homologs from aerobic archaea inherently lack the Fe-S subunit/domain called δ, which harbors two [4Fe-4S] clusters [30] [34], presumably as an evolutionary consequence of one protein adaptation strategy occurring under permanently oxidative conditions. "
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    Full-text · Article · Sep 2010 · Archaea
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    • "All other known syntrophic propionate degraders oxidize propionate to acetate plus CO 2. They use the methylmalonyl-CoA pathway which generates per molecule propionate one ATP via substrate level phosphorylation and three electron pairs by: (i) oxidation of succinate to fumarate (E°′ = +30 mV), (ii) oxidation of malate to oxaloacetate (E°′ = -176 mV), and (iii) pyruvate conversion to acetyl- CoA and CO2 (E°′ = -470 mV) (Fig. 2). The latter step can easily be coupled to proton reduction (E°′ = -414 mV) or CO2 (E°′ = -432 mV) reduction (Thauer et al., 1977) via ferredoxin, as anaerobic bacteria generally contain pyruvate : ferredoxin oxidoreductases (Chabrière et al., 1999). Oxidation of succinate and malate with protons would require hydrogen partial pressures of 10 -15 and 10 -8 atm respectively (Schink, 1997). "

    Full-text · Article · Jan 2010
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