Serine hydrolase

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

See also

• Activity based proteomics
• Alpha/beta hydrolase fold
• Amide
• Enzyme
• Ester
• List of enzymes
• Thioester