Abstract
The intriguing deactivation of the cytochrome P450 (CYP) 2B4 enzyme induced by mutation of a single residue, Phe429 to His, is explored by quantum mechanical/molecular mechanical calculations of the O-OH bond activation of the (Fe 3+OOH) - intermediate. It is found that the F429H mutant of CYP 2B4 undergoes homolytic instead of heterolytic O-OH bond cleavage. Thus, the mutant acquires the following characteristics of a heme oxygenase enzyme: (a) donation by His429 of an additional NH - -S H-bond to the cysteine ligand combined with the presence of the substrate retards the heterolytic cleavage and gives rise to homolytic O-OH cleavage, and (b) the Thr302/water cluster orients nascent OH • and ensures efficient meso hydroxylation.
Original language | English |
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Pages (from-to) | 4053-4056 |
Number of pages | 4 |
Journal | Journal of the American Chemical Society |
Volume | 134 |
Issue number | 9 |
DOIs | |
State | Published - 7 Mar 2012 |