Interactions of papaya proteinase IV with inhibitors

FEBS Lett. 1990 Mar 12;262(1):58-60. doi: 10.1016/0014-5793(90)80153-a.

Abstract

Papaya proteinase IV (PPIV) is not inhibited by chicken cystatin, or human cystatins A or C, unlike most other proteinases of the papain superfamily. The enzyme inactivates chicken cystatin and human cystatin C by limited proteolysis of the glycyl bond previously shown to be involved in the inhibitory inactivity of the cystatins, but has no action on cystatin A. Contamination of commercial crystalline papain with PPIV accounts for the limited proteolysis of cystatins by 'papain' reported previously. PPIV is slowly bound by human alpha 2-macroglobulin. The enzyme is irreversibly inactivated by E-64, and by peptidyl diazomethanes containing glycine in P1 and a hydrophobic side-chain in P2. The reaction of PPIV with iodoacetate is extremely slow. PPIV is inhibited by peptide aldehydes despite the presence of bulky sidechains in P1, suggesting that these reversible inhibitors do not bind as substrate analogues.

MeSH terms

  • Binding Sites
  • Cystatins / pharmacology
  • Cysteine Endopeptidases*
  • Cysteine Proteinase Inhibitors*
  • Papain / analysis
  • Papain / antagonists & inhibitors*
  • Protease Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • alpha-Macroglobulins / analysis

Substances

  • Cystatins
  • Cysteine Proteinase Inhibitors
  • Protease Inhibitors
  • alpha-Macroglobulins
  • Cysteine Endopeptidases
  • Papain
  • glycyl endopeptidase