The activation pathway of procarboxypeptidase B from porcine pancreas: Participation of the active enzyme in the proteolytic processing

Research output: Contribution to journalArticleResearchpeer-review

24 Citations (Scopus)

Abstract

The activation process of porcine pancreatic procarboxypeptidase B (pro‐CPB) has been studied in detail by a number of complementary methodologies, and a description of the molecular events that lead to the generation of active carboxypeptidase B (CPB) has been deduced. The generated CPB participates in the degradation of its own activation segment by excising C‐terminal residues from fragments produced by tryptic proteolysis. The trimming action of CPB is, however, not essential for the release of a fully functional enzyme, in contrast to what was previously reported for porcine procarboxypeptidase A (pro‐CPA). In the model presented here, the activation process is solely dependent on the first tryptic cleavage, at the limit between the activation segment and the enzyme region, and the former piece loses all of its inhibitory capacity once severed from the proenzyme. The use of heterologous inhibitors of CPB activity during the study of the tryptic activation process of pro‐CPB has been required for the capture of short‐lived, otherwise nondetectable, intermediates. This has allowed a complete description of the process and shown that the first proteolytic action of trypsin can also take place on a second target bond. Structural considerations that take into account the three‐dimensional structures of the A and B forms of the proenzymes lead us to propose that the differences in conformation at the region that connects the globular activation domain to the enzyme are the main responsible elements for the differences observed in the activation processes of both proenzymes. Copyright © 1995 The Protein Society
Original languageEnglish
Pages (from-to)1792-1800
JournalProtein Science
Volume4
Issue number9
DOIs
Publication statusPublished - 1 Jan 1995

Keywords

  • activation domain
  • activation segment
  • inhibition mechanism
  • limited proteolysis
  • procarboxypeptidase
  • zymogen

Fingerprint Dive into the research topics of 'The activation pathway of procarboxypeptidase B from porcine pancreas: Participation of the active enzyme in the proteolytic processing'. Together they form a unique fingerprint.

  • Cite this