Sandbox Reserved 921

Function

The Fatty acid amide hydrolase is an integral protein that cleaves fatty acid amides at the carbon-oxygen double bond in the amide functional group. The lipid-degrading activity of FAAH derives from its unusual , consisting of Ser241, Ser217, and Lys142. The hydrogen bonding between the three amino acid residues allows for a partial negative charge at , which acts as a nucleophile in the enzymatic reaction. The Ser241 residue binds with the carbon in the amide group, cleaves the fatty acid amide, and is protonated by water. The inhibitor used covalently binds to Ser241 disrupting the catalytic triad active site and leaving the hydrolase inactive. Without the enzyme FAAH active, anandamide accumulates, resulting in pain relief due to its interaction with the CB1 and CB2 cannabinoid receptors.

Structure

The of FAAH reveals two openings directly accessible by the inner layer of the lipid bilayer. These (MAC) are each proceed by a respective membrane binding cap. This sturdy flap appears to be loosened by the presence of five positively charged residues, and the each MAC is remains conformation-stable by a salt bridge. The membrane access channel leads to the active site, which is flanked by the both the (ABP and CP). The cytosolic port is a lengthy, flexible loop that leads directly into the cytoplasm, allowing the deacylated amine to enter the cell.