Oxidative Degradation of Pyruvate Formate-Lyase

The reaction mechanisms of oxidative degradation of the anaerobic radical enzyme pyruvate formate-lyase (PFL) have been examined at the theoretical hybrid Hartree−Fock/density functional theory level B3-LYP. It is concluded that the most likely scenario involves O₂ addition at the glycyl radical site, followed by H^• abstraction/transfer from C419 and subsequent rearrangements to generate an α-hydroxyglycine and the sulfinyl radical R−SO^•, observed by EPR spectroscopy. In addition, the present model accounts for alternative fragmentations observed in wild-type PFL, and the formation and degradation of Gly−O-O^• in the absence of C419 (as observed in C419A and C419AC418A mutants).