Crystal structure of the free radical intermediate of pyruvate:ferredoxin oxidoreductase.
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Chabriere E, Vernede X, Guigliarelli B, Charon MH, Hatchikian EC, Fontecilla-Camps JC
Crystal structure of the free radical intermediate of pyruvate:ferredoxin oxidoreductase.
Science. 2001 Dec 21;294(5551):2559-63.
- PubMed ID
- 11752578 [ View in PubMed]
- 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 A-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.