Advances in metallo‐procarboxypeptidases: Emerging details on the inhibition mechanism and on the activation process

Francesc X. AVILÉS, Josep VENDRELL, Alicia GUASCH, Miquel COLL, Robert HUBER

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70 Citations (Scopus)

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 metallocarboxypeptidases, 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 α‐helical connecting region and the stability of its contacts with the enzyme account for the different activation properties of A and B zymogens. Copyright © 1993, Wiley Blackwell. All rights reserved
Original languageEnglish
Pages (from-to)381-389
JournalEuropean Journal of Biochemistry
Volume211
Issue number3
DOIs
Publication statusPublished - 1 Jan 1993

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