Serine hydrolase superfamily (SH)

The serine hydrolase superfamily is one of the largest and most diverse enzyme classes in mammals, comprising over 200 members including proteases, lipases, esterases, and thioesterases. These enzymes are characterized by a conserved catalytic mechanism involving a nucleophilic serine residue, often found within a Gly-X-Ser-X-Gly consensus motif, which forms a covalent acyl-enzyme intermediate with substrates. They play critical roles in virtually every physiological process, from blood coagulation and digestion to neurotransmission and immune response. Due to their central roles in health and disease, serine hydrolases are major therapeutic targets for conditions such as diabetes (DPP-4 inhibitors), obesity (lipase inhibitors), and Alzheimer's disease (acetylcholinesterase inhibitors). However, the structural similarity across the superfamily poses significant challenges for achieving drug selectivity and avoiding off-target safety concerns.

Other names

Serine-dependent enzymesSerine proteasesSerine esterasesSerine lipasesSerine-dependent hydrolases

Inhibition of the nucleophilic serine residue within the catalytic triad (typically Ser-His-Asp) of the enzyme's active site, often through covalent modification (e.g., phosphorylation by organophosphates or carbamylation by carbamates).