Sandbox Reserved 921: Difference between revisions
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'''Fatty Acid Amide Hydrolase''' | '''Fatty Acid Amide Hydrolase''' | ||
[[Image:CatalyticTriadProteopedia.png|100 px|left|thumb| | [[Image:CatalyticTriadProteopedia.png|100 px|left|thumb|Ser, Ser, Lys Catalytic Triad]] | ||
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== Function == | == Function == | ||
The Fatty acid amide hydrolase <scene name='57/573135/4j5p_dimer/3'>dimer</scene> 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 <scene name='57/573135/Catalytic_triad/2'>catalytic triad</scene>, consisting of Ser241, Ser217, and Lys142. The hydrogen bonding between the three amino acid residues allows for a partial negative charge at <scene name='57/573135/Ser241_4j5p/1'>Ser241</scene>, 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. | The Fatty acid amide hydrolase <scene name='57/573135/4j5p_dimer/3'>dimer</scene> 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 <scene name='57/573135/Catalytic_triad/2'>catalytic triad</scene>, consisting of Ser241, Ser217, and Lys142. The hydrogen bonding between the three amino acid residues allows for a partial negative charge at <scene name='57/573135/Ser241_4j5p/1'>Ser241</scene>, 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 <scene name='57/573136/Starting_view/1'>surface</scene> of FAAH reveals two openings directly accessible by the inner layer of the lipid bilayer. These <scene name='57/573136/Membrane_access_channel/4'>membrane access channels</scene> (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 <scene name='57/573136/Cytosolic_port/2'>acyl chain binding pocket and cytosolic port </scene> (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. | |||