Modification of enzymes by protein folding memory

Abstract

Propeptides, which are N‐terminal or C‐terminal domain of most proteases and lipases, are cleaved off in the protein maturation steps. Some propeptides are known to function as an intramolecular chaperone to facilitate the folding of their active region. Protein folding memory means a phenomenon in which a mutated propeptide alters the conformation of the enzymatically active region without mutations in the coding region and thereby the activity and thermal stability are altered. However, there are few examples showing the modification of enzymes by protein folding memory.In this study, we attempted to modify carboxypeptidase Y (CPY) by introducing mutations into its propeptide. CPY with the mutated propeptide showed the higher activity and thermal stability than that with wild type propeptide [1]. This result indicated that two CPYs with the identical amino acid sequences were folded into different structures by the different propeptides. Furthermore, we recently have investigated protein folding memory using Rhizopus oryzae lipase (ROL) as the second model. ROL whose propeptide was replaced by the propeptide of ROL‐related lipase showed the higher activity than wild type ROL. Then, the mechanism causing the higher activity was investigated.