Gaining insight into the chemistry of lipoxygenases: a computational investigation into the catalytic mechanism of (8R)-lipoxygenase

摘要: Lipoxygenases (LOXs) are ubiquitous in nature and catalyze a range of life-essential reactions within organisms. In particular they critical to the formation eicosanoids, which for normal cell function. However, number important questions about reactivity mechanism these enzymes still remain. Specifically, although initial step LOXs has been well studied, little is known subsequent steps. Thus, with use quantum mechanical/molecular mechanical approach, complete catalytic (8R)-LOX was investigated. The results have provided better understanding general chemistry as whole. particular, from comparisons soybean LOX-1, it appears that proton-coupled electron transfer may be very similar among all LOXs. Furthermore, appear undergo multistate where potential spin inversion an occur either attack O2 or regeneration active site. Lastly, shown explicit modeling environment, center likely occurs via rotation intermediate followed by outer-sphere \(\rm{H^\cdot}\) opposed “purple intermediate” complex.