serine195

Serine195 (Ser195) is the serine residue numbered 195 in the catalytic center of many serine proteases within the chymotrypsin family. This numbering, based on chymotrypsin, is a standard reference in describing the active-site architecture of related enzymes, including trypsin and other endopeptidases.

In serine proteases, Ser195 is part of the catalytic triad that also includes His57 and Asp102. The hydroxyl group of Ser195 acts as a nucleophile, attacking the carbonyl carbon of the substrate's peptide bond to form a covalent acyl-enzyme intermediate. His57 serves as a general base, activating Ser195 by abstracting a proton, while Asp102 stabilizes the positively charged His57 during the reaction. The transition state is stabilized by an oxyanion hole, formed mainly by backbone amide groups of Gly193 and Ser195, which helps lower the activation energy of the reaction.

The catalytic cycle proceeds with formation of the acyl-enzyme intermediate, followed by deacylation where a water molecule, activated by His57, attacks the acyl-enzyme to release the cleaved peptide and regenerate the active site. Substrate specificity arises from the binding pocket surrounding the active site, of which Ser195 is central to catalysis rather than determine specificity alone.

Mutations at Ser195 typically disrupt protease activity, underscoring its essential role in catalysis. Ser195 remains a focal point in structural and mechanistic studies of serine proteases, and is frequently cited in discussions of enzyme mechanism and inhibitor design.