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The proprotein convertases

D F Steiner1

  • 1Howard Hughes Medical Institute, University of Chicago, 5841 South Maryland Avenue, MC 1028, Chicago, IL 60637, USA. dfsteine@midway.uchicago.edu

Current Opinion in Chemical Biology
|July 17, 1998
PubMed
Summary
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Subtilisin-like proprotein convertases (SPCs) like Furin, PC2, and PC1/PC3 are key enzymes for processing hormones and neuropeptides. Carboxypeptidase E and peptidylglycine alpha-amidating monooxygenase are also crucial for peptide maturation.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • The secretory pathway relies on specific enzymes for protein processing.
  • Subtilisin-like proprotein convertases (SPCs) are major endoproteolytic enzymes involved in this pathway.
  • Understanding these enzymes is crucial for comprehending hormone and neuropeptide regulation.

Purpose of the Study:

  • To review the roles of key enzymes in the endoproteolytic processing of secretory pathway proteins.
  • To highlight the functions of SPCs, Carboxypeptidase E (CPE), and peptidylglycine alpha-amidating monooxygenase (PAM).
  • To discuss recent insights into the mechanisms of these processing enzymes.

Main Methods:

  • Review of existing literature on SPCs, CPE, and PAM.
  • Analysis of gene disruption experiments and naturally-occurring mutations.

Related Experiment Videos

  • Incorporation of recent X-ray crystallography data for PAM.
  • Main Results:

    • Furin (SPC1) is a major enzyme in the constitutive secretory pathway, with well-studied localization and autoactivation.
    • PC2 (SPC2) and PC1/PC3 (SPC3) are essential for processing various hormone and neuropeptide precursors.
    • CPE is necessary for efficient processing of proinsulin and other precursors by removing basic residues.
    • PAM is involved in the amidation of biologically active peptides, with copper playing a role in its mechanism.

    Conclusions:

    • SPCs, CPE, and PAM are critical components of the secretory pathway's proteolytic processing machinery.
    • These enzymes collectively ensure the generation of mature, biologically active hormones and neuropeptides.
    • Ongoing research, including structural studies, continues to elucidate their precise functions and mechanisms.