Sandbox Reserved 921
From Proteopedia
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== Introduction == | == Introduction == | ||
| - | [http://en.wikipedia.org/wiki/Fatty_acid_amide_hydrolase Fatty acid amide hydrolase] (FAAH) is the primary catabolic enzyme for the degradation of | + | [http://en.wikipedia.org/wiki/Fatty_acid_amide_hydrolase Fatty acid amide hydrolase] (FAAH) is the primary catabolic enzyme for the degradation of [http://en.wikipedia.org/wiki/Fatty_acid_amide fatty acid amides]. FAAH is most commonly known for the degradation of [http://en.wikipedia.org/wiki/Anandamide anandamide], which is an endocannabinoid that activates the CB1 and CB2 [http://en.wikipedia.org/wiki/Cannabinoid_receptor cannabinoid receptors]. When CB1 and CB2 cannabinoid receptors are active the receptors affect appetite, sleep, and relief of pain. The ability to inhibit FAAH has been widely investigated for possible pain relief medication. A recent study on FAAH inhibitors combined an irreversible bond at Cys269 and a reversible bond at Ser241 of the active site.<ref name="Most Recent Study">PMID:23581831</ref> A humanized rat variant of FAAH was inhibited and the mice displayed an increase in endogenous brain levels of FAAH substrates for over six hours. This is the first step towards developing a long lasting pain relief medication by inhibiting FAAH. |
<StructureSection load='4J5P' size='340' side='right' caption='4J5P; K and L of 1MT5' scene='57/573135/4j5p_dimer/3'> | <StructureSection load='4J5P' size='340' side='right' caption='4J5P; K and L of 1MT5' scene='57/573135/4j5p_dimer/3'> | ||
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==Structure== | ==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 <scene name='57/573136/Starting_view/1'>surface</scene> of FAAH reveals two openings directly accessible by the inner layer of the [http://en.wikipedia.org/wiki/Lipid_bilayer 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 each MAC remains conformation-stable by a salt bridge. The membrane access channel leads to the active site, which is flanked by 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 [http://en.wikipedia.org/wiki/Cytoplasm cytoplasm], allowing the deacylated amine to enter the cell. |
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<ref name="Most Recent Study"/> | <ref name="Most Recent Study"/> | ||
<references/> | <references/> | ||
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| - | == External Resources == | ||
Revision as of 18:14, 4 April 2014
| This Sandbox is Reserved from Jan 06, 2014, through Aug 22, 2014 for use by the Biochemistry II class at the Butler University at Indianapolis, IN USA taught by R. Jeremy Johnson. This reservation includes Sandbox Reserved 911 through Sandbox Reserved 922. |
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Fatty Acid Amide Hydrolase
Introduction
Fatty acid amide hydrolase (FAAH) is the primary catabolic enzyme for the degradation of fatty acid amides. FAAH is most commonly known for the degradation of anandamide, which is an endocannabinoid that activates the CB1 and CB2 cannabinoid receptors. When CB1 and CB2 cannabinoid receptors are active the receptors affect appetite, sleep, and relief of pain. The ability to inhibit FAAH has been widely investigated for possible pain relief medication. A recent study on FAAH inhibitors combined an irreversible bond at Cys269 and a reversible bond at Ser241 of the active site.[1] A humanized rat variant of FAAH was inhibited and the mice displayed an increase in endogenous brain levels of FAAH substrates for over six hours. This is the first step towards developing a long lasting pain relief medication by inhibiting FAAH.
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References
- ↑ 1.0 1.1 Otrubova K, Brown M, McCormick MS, Han GW, O'Neal ST, Cravatt BF, Stevens RC, Lichtman AH, Boger DL. Rational design of Fatty Acid amide hydrolase inhibitors that act by covalently bonding to two active site residues. J Am Chem Soc. 2013 Apr 24;135(16):6289-99. doi: 10.1021/ja4014997. Epub 2013 Apr, 12. PMID:23581831 doi:http://dx.doi.org/10.1021/ja4014997
