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Crystal Structure of the Free Radical Intermediate of Pyruvate:Ferredoxin Oxidoreductase
Eric Chabrière,13Xavier Vernède,1Bruno Guigliarelli,2Marie-Hélène Charon,1E. Claude Hatchikian,2Juan C. Fontecilla-Camps1*
In anaerobic organisms, the decarboxylation of pyruvate, a crucial
component of intermediary metabolism, is catalyzed by themetalloenzyme
pyruvate: ferredoxin oxidoreductase (PFOR) resultingin the
generation of low potential electrons and the subsequentacetylation of
coenzyme A (CoA). PFOR is the only enzyme for whicha stable acetyl
thiamine diphosphate (ThDP)-based free radicalreaction
intermediate has been identified. The 1.87 Å-resolutionstructure of
the radical form of PFOR from Desulfovibrio africanusshows
that, despite currently accepted ideas, the thiazole ringof the ThDP
cofactor is markedly bent, indicating a drastic reductionof its
aromaticity. In addition, the bond connecting the acetylgroup to ThDP
is unusually long, probably of the one-electrontype already described
for several cation radicals but not yetfound in a biological system.
Taken together, our data, alongwith evidence from the literature,
suggest that acetyl-CoA synthesisby PFOR proceeds via a condensation
mechanism involving acetyl(PFOR-based) and thiyl (CoA-based) radicals.
1 Laboratoire de Cristallographie et
Cristallogenèse des Protéines, Institut de Biologie
Structurale Jean-Pierre Ebel, Commissariat à l'Energie Atomique,
Université Joseph Fourier, CNRS, 41, rue Jules Horowitz, 38027 Grenoble Cedex 1, France.
2 Unité de
Bioenérgetique et Ingénerie des Protéines, Institut
de Biologie Structurale et Microbiologie, CNRS, 31, chemin J. Aiguier,
13402 Marseilles, France.
3 Laboratoire de
Cristallographie et Modélisation des Matériaux
Minéraux et Biologiques, Unité Mixte de Recherche 7036 CNRS, Université Henri Poincaré, Nancy 1B.P. 239, 54506 Vandoeuvre-les-Nancy, France.
*
To whom correspondence should be addressed. E-mail:
juan{at}lccp.ibs.fr
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
Perry A. Frey (21 December 2001) Science294 (5551), 2489.
[DOI: 10.1126/science.1067916] |Summary »|Full Text »|PDF »
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