Serine Hydrolase

The serine hydrolase superfamily is one of the largest known enzyme families comprising approximately ~200 enzymes or 1% of the genes in the human proteome. A characteristic defining feature of this superfamily is the presence of an active site nucleophilic serine that is used for the hydrolysis of substrates. Catalysis proceeds by the formation of an acyl-enzyme intermediate through this serine, followed by water/hydroxide-induced saponification of the intermediate and regeneration of the enzyme. Unlike other non-catalytic serines, the nucleophilic serine of these hydrolases is typically activated by a proton relay involving an acidic residue (e.g. aspartate or glutamate) and a basic residue (usually histidine) although variations on this mechanism exist.

This family includes:

• serine proteases, including trypsin, chymotrypsin, and subtilisin
• Extracellular lipases, including pancreatic lipase, hepatic lipase, gastric lipase, endothelial lipase, and lipoprotein lipase
• Intracellular lipases, including hormone sensitive lipase, monoacylglycerol lipase, adipose triglyceride lipase, and diacylglycerol lipase
• Cholinesterases, including acetylcholinesterase and butyrylcholinesterase
• Small molecule thioesterases, including fatty acid synthase and the acyl-CoA thioesterases
• Some phospholipases, including phospholipase A2 and platelet activating factor acetylhydrolase
• Protein and glycan hydrolases, including protein phosphate methylesterase 1, acyloxyacyl hydrolase and sialic acid acetylesterase
• Some amidases, including fatty acid amide hydrolase
• Some peptidases, including dipeptiyl peptidase 4, fibroblast activation protein, and prolylendopeptidase