title: Advances in metallo-procarboxypeptidases. Emerging details on the inhibition mechanism and on the activation process.
abstract: Our knowledge on the structure and functionality of pancreatic carboxypeptidases is rapidly expanding to include that of their zymogen forms. The recent application of fast and mild isolation procedures, together with modern molecular genetic and biochemical-biophysical characterization approaches, has provided a clearer view of the basic structures and functional states in which these zymogens occur, and their evolutionary relationships. The same holds for related metallo-carboxypeptidases, either in the pro or active forms, that have been isolated and characterized in non-digestive fluids and tissues, where they probably play an important role in protein and peptide processing. The determination of the three-dimensional structure of the A and B pancreatic zymogens has revealed the molecular determinants of their inactivity and proteolytic activation. The folding of their 95-residue activation segment in a globular N-terminal domain (74-81 residues) and in a connecting region (20-14 residues), and the specific contacts of these pieces with the substrate binding sites of the enzyme, are important factors in zymogen inhibition. On the other hand, the different length of the alpha-helical connecting region and the stability of its contacts with the enzyme account for the different activation properties of A and B zymogens.
authors.affiliation: Departament de Bioquímica (Fac. Ciències), Universitat Autònoma de Barcelona, Spain.
authors.forename: F X
authors.initials: FX
authors.lastname: Avilés
authors.forename: J
authors.initials: J
authors.lastname: Vendrell
authors.forename: A
authors.initials: A
authors.lastname: Guasch
authors.forename: M
authors.initials: M
authors.lastname: Coll
authors.forename: R
authors.initials: R
authors.lastname: Huber
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004789:Enzyme Activation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation
chemical_list: D002268:Carboxypeptidases