English: Serine proteases operate by a two-step catalytic mechanism. First, the substrate (blue) is attacked by the catalytic triad (red) to form an acyl-enzyme intermediate. The intermediate is typically resolved by hydrolysis by water. However, when the reactive centre loop (RCL) of a serpin is attacked, the conformational change (blue arrow) pulls the catalytic triad out of position, preventing it from completing catalysis. (Based on PDB: 1K9O, 1EZX​)