Three-state thermal unfolding of onconase.

Abstract

Onconase is a member of the ribonuclease A superfamily currently in phase IIIb clinical trials as a treatment for malign mesothelioma due to its cytotoxic activity selective against tumor-cells. In this work, we have studied the equilibrium thermal unfolding of onconase using a combination of several structural and biophysical techniques. Our results indicate that at least one significantly populated intermediate, which implies the exposure of hydrophobic surface and significant changes in the environment around Trp3, occurs during the equilibrium unfolding process of this protein. The intermediate begins to populate at about 30° below the global unfolding temperature, reaching a maximum population of nearly 60%, 10° below the global unfolding temperature.

• Authors: Salvador Casares-Atienza, Ulrich Weininger, Ana Cámara-Artigas, Jochen Balbach, Maria M Garcia-Mira
• Journal: Biophysical chemistry (Biophys Chem) Vol. 159 Issue 2-3 Pg. 267-74 (Dec 2011) ISSN: 1873-4200 [Electronic] Netherlands
• PMID: 21840114 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Amphibian Proteins
• Antineoplastic Agents
• Ribonucleases
• ranpirnase

Topics

• Amino Acid Sequence
• Amphibian Proteins (chemistry)
• Animals
• Antineoplastic Agents (chemistry)
• Models, Molecular
• Molecular Sequence Data
• Protein Unfolding
• Rana pipiens (metabolism)
• Ribonucleases (chemistry)
• Temperature