Sandbox Reserved 911: Difference between revisions
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Mutagenesis and inhibitor studies have shown that FAAH has a <scene name='57/573125/2vya/6'>Ser-Ser-Lys catalytic triad</scene>, consisting of S241, S217, and K142. Ser-Ser-Lys catalytic triads are not often seen in hydrolases, making FAAH an enzyme of interest for additional research to better determine how proteins with this catalytic triad function. S241 acts as the catalytic nucleophile for the cleavage of amide bonds. (IMT5) | Mutagenesis and inhibitor studies have shown that FAAH has a <scene name='57/573125/2vya/6'>Ser-Ser-Lys catalytic triad</scene>, consisting of S241, S217, and K142. Ser-Ser-Lys catalytic triads are not often seen in hydrolases, making FAAH an enzyme of interest for additional research to better determine how proteins with this catalytic triad function. S241 acts as the catalytic nucleophile for the cleavage of amide bonds. (IMT5) | ||
FAAH requires two water molecules in its active site to properly position and cleave amide bonds. One water molecule (W1) deacylates the substrate, and the other (W2) helps coordinate W1 through the catalytic K142. (3LJ6) | FAAH requires two water molecules in its active site to properly position and cleave amide bonds. One water molecule (W1) deacylates the substrate, and the other (W2) helps coordinate W1 through the catalytic K142. (3LJ6) | ||
[[Image: | |||
[[Image:Catalytic_triad2.png]] | |||
==Relationship to other proteins== | ==Relationship to other proteins== | ||
The hydrolytic water molecules important to FAAH's function suggest an evolutionary relationship of this hydrolase to other enzymes. The structures of other [http://en.wikipedia.org/wiki/Serine_hydrolase serine hydrolases] also display a catalytic water molecule in their active sites. Because hydrolases that are non-homologous to FAAH also require a water molecule to cleave bonds, researchers have inferred that a functional convergance has developed between amidase signature enzymes (such as FAAH) and other classes of serine proteases. (3LJ6) | The hydrolytic water molecules important to FAAH's function suggest an evolutionary relationship of this hydrolase to other enzymes. The structures of other [http://en.wikipedia.org/wiki/Serine_hydrolase serine hydrolases] also display a catalytic water molecule in their active sites. Because hydrolases that are non-homologous to FAAH also require a water molecule to cleave bonds, researchers have inferred that a functional convergance has developed between amidase signature enzymes (such as FAAH) and other classes of serine proteases. (3LJ6) | ||
[[Image:Water_image.png|400 px|left|thumb|FAAH catalytic site with water molecules bound]] | |||
This evidence of convergent evolution between FAAH and other amidase signature enzymes supports the [http://euch6f.chem.emory.edu/burgidunitz.html Bürgi-Dunitz theory]. This concept proposes that nucleophiles tend to follow a specific trajectory when attacking a carbonyl, resulting in many enzyme mechanisms having the same angle between an incoming nucleophile and the carbonyl it attacks. Research showing water molecules in the active sites of enzymes suggests that these water molecules are specifically positioned to force the nucleophile to approach at the exact [http://3.bp.blogspot.com/-NvsQyVPnLIw/UO91-BQTVgI/AAAAAAAAExw/-seGZcjU3DE/s400/burgi-duntz+trajectory.png "Bürgi-Dunitz angle"] of 107°. The determination that FAAH also has water molecules in its active site, helping the nucleophile to attack the amide carbonyl at a specific angle, adds additional support to the Bürgi-Dunitz theory. (3LJ6) | This evidence of convergent evolution between FAAH and other amidase signature enzymes supports the [http://euch6f.chem.emory.edu/burgidunitz.html Bürgi-Dunitz theory]. This concept proposes that nucleophiles tend to follow a specific trajectory when attacking a carbonyl, resulting in many enzyme mechanisms having the same angle between an incoming nucleophile and the carbonyl it attacks. Research showing water molecules in the active sites of enzymes suggests that these water molecules are specifically positioned to force the nucleophile to approach at the exact [http://3.bp.blogspot.com/-NvsQyVPnLIw/UO91-BQTVgI/AAAAAAAAExw/-seGZcjU3DE/s400/burgi-duntz+trajectory.png "Bürgi-Dunitz angle"] of 107°. The determination that FAAH also has water molecules in its active site, helping the nucleophile to attack the amide carbonyl at a specific angle, adds additional support to the Bürgi-Dunitz theory. (3LJ6) | ||
