Serpins are remarkable and unique proteins in being able to spontaneously fold into a
metastable conformation without the aid of a chaperone or prodomain. This metastable
conformation is essential for inhibition of proteinases, so that massive serpin conformational
change, driven by the favorable energetics of relaxation of the metastable conformation to
the more stable one, can kinetically trap the proteinase-serpin acylenzyme intermediate.
Failure to direct folding to the metastable conformation would lead to inactive, latent serpin …