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

Authors :
Chabrière, Eric
Charon, Marie–Helene
Volbeda, Anne
Pieulle, Laetitia
Hatchikian, Etienne Claude
Fontecilla–Camps, Juan–Carlos
Source :
Nature Structural and Molecular Biology; February 1999, Vol. 6 Issue: 2 p182-190, 9p
Publication Year :
1999

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 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.

Details

Language :
English
ISSN :
15459993 and 15459985
Volume :
6
Issue :
2
Database :
Supplemental Index
Journal :
Nature Structural and Molecular Biology
Publication Type :
Periodical
Accession number :
ejs25307049
Full Text :
https://doi.org/10.1038/5870