Rational Enzyme Design: Computer Modeling and Site-directed Mutagenesis for the Modification of Catalytic Specificity in Organophosphorus Hydrolase

Abstract

So, where do natural products fit in this brave new world? Two words are all that are needed to answer this, quality and utility. We should remember that naturalproducts chemistries represent the greatest sources of scaffold diversity and that these scaffolds are pharmacophore rich, i.e., the molecules are biologically relevant and have been conserved through an evolutionary process on the basis that they confer competitive advantage on the producing organism. The biological relevance of these molecules is manifest in growth and differentiation modulation, in enzyme inhibition or regulation, in receptor agonism or antagonism -biological events common to human disease processes. The ultimate test of quality and utility is market sales, at the very pinnacle of which is Organophosphorus neurotoxins are widely used as insecticides in crop production, municipal hygiene, and disease vector control as well as providing the major classes of chemical warfare neuro-