Ser195

Ser195 denotes the serine residue at position 195 in the chymotrypsin numbering scheme, a widely used reference frame for serine proteases such as chymotrypsin, trypsin, and elastase. The residue is highly conserved and commonly serves as the catalytic nucleophile in the protease active site, within the catalytic triad that also includes Histidine 57 and Aspartate 102 (in chymotrypsin numbering).

During catalysis, His57 acts as a base to activate Ser195 by abstracting a proton from its hydroxyl group, generating a reactive alkoxide. Ser195 then attacks the substrate’s carbonyl carbon, forming a tetrahedral intermediate that is stabilized by the oxyanion hole, typically formed by backbone amide NHs of Ser195 and nearby residues such as Gly193. Collapse of this intermediate yields an acyl-enzyme and a short-lived amine or peptide fragment. In the deacylation step, a water molecule, activated by His57, attacks the acyl-enzyme, forming a second tetrahedral intermediate that is again stabilized by the oxyanion hole and subsequently collapses to release the parent carboxylate and regenerate Ser195.

Ser195 is located in the protease's substrate-binding groove and is part of the S1 specificity pocket that determines substrate preference. Its high degree of conservation across the serine protease family reflects its central role in catalysis. Mutations at Ser195 typically lead to substantial loss of catalytic activity, reflecting its essential nucleophilic function.

When referenced in literature, Ser195 is often understood within the chymotrypsin numbering system. In proteins outside this family or using different sequence alignments, the equivalent residue may occupy a different position, and numbering should be interpreted in context.