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 sitenucleophilicserine 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.