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Interaction of onconase with the human ribonuclease inhibitor protein

Rebecca F Turcotte1, Ronald T Raines2

  • 1Medical Scientist Training Program and Biophysics Graduate Program, University of Wisconsin-Madison, Madison, WI, 53706, USA.

Biochemical and Biophysical Research Communications
|October 22, 2008
PubMed

Insights

The interaction between cytotoxic ribonuclease onconase (ONC) and ribonuclease inhibitor (RI) was measured. ONC

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • The ribonuclease A superfamily exhibits tight protein-protein interactions with ribonuclease inhibitor (RI).
  • Cytotoxicity of some superfamily members is linked to their ability to evade RI.
  • Onconase (ONC), a cytotoxic ribonuclease, is in clinical trials for malignant mesothelioma.

Purpose of the Study:

  • To quantify the inhibition of onconase (ONC) ribonucleolytic activity by ribonuclease inhibitor (RI).
  • To characterize the binding affinity between ONC and RI.

Main Methods:

  • Enzyme activity assays were used to measure the inhibition of ONC by RI.
  • The inhibition constant (K_i) was determined under specific solution conditions.

Main Results:

  • The inhibition of ONC's ribonucleolytic activity by RI was measured for the first time.
  • The inhibition occurred with a K_i of 0.15 μM in a low salt concentration solution.

Conclusions:

  • This study provides the first quantitative measurement of ONC inhibition by RI.
  • The determined inhibition constant offers insight into the molecular interactions governing ONC's cytotoxic potential.

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