title: Cutting at the right place--the importance of selective limited proteolysis in the activation of proproteinase E.
abstract: Proteinase E is a proteolytic enzyme which belongs to a distinct subfamily of chymotrypsin-like serine endopeptidases. Its proform from the bovine pancreatic system has been structurally analyzed by X-ray crystallography for the intact native form, with a 11-residue N-terminal activation peptide, in a ternary complex with chymotrypsinogen C and procarboxypeptidase A [Gomis-Rüth, F. X., Gómez, M., Bode, W., Huber, R. & Avilés, F. X. (1995) The three-dimensional structure of the native ternary complex of bovine pancreatic procarboxypeptidase A with proproteinase E and chymotrypsinogen C, EMBO J. 14, 4387-4394]. Also for a N-terminally truncated form, lacking the first 13 residues and called subunit 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 structures are well defined by electron density, except for the first 7 residues of subunit III. However, both structures present large deviations of up to 2 nm in several regions, indicating that they correspond to two quite distinct states of low free energy, influenced by very few contacts made via the N-terminal segment. As no structure of an active 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.
authors.affiliation: Departament de Biologia Molecular i Cellular, Centre d'Investigaciò i Desenvolupament C.S.I.C., Barcelona, Spain.
authors.forename: F X
authors.initials: FX
authors.lastname: Gomis-Rüth
authors.forename: M
authors.initials: M
authors.lastname: Gómez-Ortiz
authors.forename: J
authors.initials: J
authors.lastname: Vendrell
authors.forename: S
authors.initials: S
authors.lastname: Ventura
authors.forename: W
authors.initials: W
authors.lastname: Bode
authors.forename: R
authors.initials: R
authors.lastname: Huber
authors.forename: F X
authors.initials: FX
authors.lastname: Avilés
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002268:Carboxypeptidases / Q000737:chemistry / Q000378:metabolism; D043422:Carboxypeptidases A; D002417:Cattle; D002919:Chymotrypsinogen / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D010450:Endopeptidases / Q000737:chemistry* / Q000378:metabolism*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010179:Pancreas / Q000201:enzymology; D010196:Pancreatic Elastase / Q000737:chemistry; D011487:Protein Conformation; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D013552:Swine
chemical_list: D004792:Enzyme Precursors; D046911:Macromolecular Substances; C096020:chymotrypsinogen C; D002919:Chymotrypsinogen; D002268:Carboxypeptidases; D010450:Endopeptidases; C035786:pro-proteinase E; D043422:Carboxypeptidases A; D012697:Serine Endopeptidases; D010196:Pancreatic Elastase