The enzyme fatty acid amide hydrolase (FAAH) plays an important role in a variety of pathophysiological conditions of mammalian nervous system. It is been identified that a human natural variant of FAAH P129T) is associated with drug abuse and dependence. We have shown that P129T mutant enzyme has wild type FAAH catalytic properties, but is more susceptible to proteolysis in vitro. In this proposal, I will determine the structure of P129T-FAAH using x-ray crystallography. With the aid of structural information, I will further investigate the molecular basis for functional alterations of P129T-FAAH. Findings from these studies will guide the development of potential therapeutics for drug addiction.
