X-ray crystallographic structure of RNase Po1 that exhibits anti-tumor activity.

Abstract

RNase Po1 is a guanylic acid-specific ribonuclease member of the RNase T1 family from Pleurotus ostreatus. We previously reported that RNase Po1 inhibits the proliferation of human tumor cells, yet RNase T1 and other T1 family RNases are non-toxic. We determined the three-dimensional X-ray structure of RNase Po1 and compared it with that of RNase T1. The catalytic sites are conserved. However, there are three disulfide bonds, one more than in RNase T1. One of the additional disulfide bond is in the catalytic and binding site of RNase Po1, and makes RNase Po1 more stable than RNase T1. A comparison of the electrostatic potential of the molecular surfaces of these two proteins shows that RNase T1 is anionic whereas RNase Po1 is cationic, so RNase Po1 might bind to the plasma membrane electrostatically. We suggest that the structural stability and cationic character of RNase Po1 are critical to the anti-cancer properties of the protein.

• Authors: Hiroko Kobayashi, Takuya Katsutani, Yumiko Hara, Naomi Motoyoshi, Tadashi Itagaki, Fusamichi Akita, Akifumi Higashiura, Yusuke Yamada, Norio Inokuchi, Mamoru Suzuki
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 37 Issue 6 Pg. 968-78 ( 2014) ISSN: 1347-5215 [Electronic] Japan
• PMID: 24882409 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• ribonuclease Po1
• Ribonuclease T1

Topics

• Amino Acid Sequence
• Antineoplastic Agents (chemistry, isolation & purification, pharmacology)
• Cell Proliferation (drug effects)
• Crystallization
• Crystallography, X-Ray
• Electrophoresis, Polyacrylamide Gel
• HL-60 Cells
• Humans
• Hydrophobic and Hydrophilic Interactions
• Molecular Sequence Data
• Pleurotus (enzymology)
• Protein Structure, Secondary
• Protein Structure, Tertiary
• Ribonuclease T1 (chemistry, isolation & purification, pharmacology)