Predicting the active site in 8R-lipoxygenase for arachidonic acid using internal coordinate mechanics approach.

摘要

Lipoxygenases (LOX) play important roles in the biosynthesis of biologically active eicosanoids form polyunsaturated fatty acids. An understanding of the structure basis of LOX family is critical for the development of LOX specific inhibitors. In this study, a computational approach, Internal Coordinate Mechanics (ICM), was applied to identify the binding site of 8R-LOX for its substrate, arachidonic acid (AA). ICM script language was used to perform ICM operations. A model of 8R-LOX: AA complex was generated. The modeling simulation results showed that the C10 of AA is positioned against the catalytic Fe atom enclosed in 8R-LOX, which favors the catalytic process of 8R-LOX. The model can explain the region-specificity and stereo-specificity of 8R-LOX. The active binding site of 8R-LOX has been defined. The result from this research will help model the interactions of protein-substrate in the LOX super family.