CUTTING AT THE RIGHT PLACE - THE IMPORTANCE OF SELECTIVE LIMITED PROTEOLYSIS IN THE ACTIVATION OF PROPROTEINASE-E

Proteinase E is a proteolytic enzyme which belongs to a distinct subfa mily of chymotrypsin-like serine endopeptidases. Its preform from the bovine pancreatic system]las been structurally analyzed by X-ray cryst allography for the intact native form, with;I Ii-residue N-terminal ac tivation peptide, in a ternary complex with chymotrypsinogen C and pro carboxypeptidase A [Gomis-Ruth, F. X., Gomez, M., Bode, W., Huber, R. & Aviles, F. X. (1995) The three-dimensional structure of the native t ernary complex of bovine pancreatic procarboxypeptidase A, with propro teinase E and chymotrypsinogen C, EMBO J. 14, 4387-4394]. Also for a N -terminally truncated form, lacking the first 13 residues and called s ubunit III, a crystal structure is available [Pignol, D., Gaboriaud,C. , Michon, T., Kerfelec, B., Chapus, C. & Fontecilla-Camps, J. C. (1994 ) Crystal structure of bovine procarboxypeptidase A-S6 subunit III, a highly structured truncated zymogen E, EMBO J. 8, 1763-1771]. Both str uctures are well defined by electron density, except for the first 7 r esidues of subunit III. However, both structures present large deviati ons of up to 2 nm in several regions, indicating that they correspond to two quite distinct states of low free energy, influenced by very fe w contacts made via the N-terminal segment. As no structure of an acti ve proteinase E is known so far, pancreatic porcine elastase has been chosen as a model for this enzyme and an activation mechanism for this distinct serine endopeptidase subfamily is proposed.