Serine hydrolases are one of the largest known enzyme classes comprising approximately ~200 enzymes or 1% of the genes in the human proteome. A defining characteristic of these enzymes is the presence of a nucleophilic serine in their active site, which 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 a catalytic triad consisting of the serine, an acidic residue (e.g. aspartate or glutamate) and a basic residue (usually histidine), although variations on this mechanism exist.
Superfamilies of serine hydrolases 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 dipeptidyl peptidase 4, fibroblast activation protein, and prolylendopeptidase