Sandbox Reserved 911: Difference between revisions

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 <ref name="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 <ref name="3LJ6"/>.