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Crystal Structure of the Free Radical Intermediate of Pyruvate:Ferredoxin Oxidoreductase

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Science  21 Dec 2001:
Vol. 294, Issue 5551, pp. 2559-2563
DOI: 10.1126/science.1066198

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Abstract

In anaerobic organisms, the decarboxylation of pyruvate, a crucial component of intermediary metabolism, is catalyzed by the metalloenzyme pyruvate: ferredoxin oxidoreductase (PFOR) resulting in the generation of low potential electrons and the subsequent acetylation of coenzyme A (CoA). PFOR is the only enzyme for which a stable acetyl thiamine diphosphate (ThDP)–based free radical reaction intermediate has been identified. The 1.87 Å–resolution structure of the radical form of PFOR from Desulfovibrio africanus shows that, despite currently accepted ideas, the thiazole ring of the ThDP cofactor is markedly bent, indicating a drastic reduction of its aromaticity. In addition, the bond connecting the acetyl group to ThDP is unusually long, probably of the one-electron type already described for several cation radicals but not yet found in a biological system. Taken together, our data, along with evidence from the literature, suggest that acetyl-CoA synthesis by PFOR proceeds via a condensation mechanism involving acetyl (PFOR-based) and thiyl (CoA-based) radicals.

  • * To whom correspondence should be addressed. E-mail: juan{at}lccp.ibs.fr

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