serinehydrolase

Serine hydrolase refers to a large and diverse superfamily of enzymes that catalyze hydrolysis reactions using a serine residue in the active site as a nucleophile. Members act on a range of substrates, including peptide bonds in proteins, ester bonds in lipids, and phosphate esters, classically forming a covalent acyl-enzyme intermediate during turnover.

Most serine hydrolases share a catalytic mechanism based on a Ser–His–Asp (or Ser–His–Glu) triad that facilitates proton transfer and nucleophilic attack. The active-site serine is typically found within a conserved motif such as Gly-X-Ser-X-Gly, sometimes referred to as the catalytic “serine elbow.” Variation in motif and surrounding structure underpins the wide substrate scope seen across the family.

Subgroups of serine hydrolases include serine proteases (for example trypsin, chymotrypsin, elastase, thrombin, and factor Xa) that cleave peptide bonds, as well as esterases, lipases, cholinesterases, and phospholipases that hydrolyze ester and phosphoester bonds. They are widely distributed across bacteria, archaea, and eukaryotes, and play essential roles in digestion, metabolism, signaling, detoxification, and tissue remodeling.

Clinical and industrial relevance is broad. Serine hydrolases are common drug targets; inhibitors such as organophosphates covalently modify the active serine, while reversible inhibitors are used therapeutically (for example, cholinesterase inhibitors in neurological disorders). The family also features in biocatalysis and biodegradation, highlighting their importance in biology and industry.