title: 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.affiliation: School of Pharmacy, Nihon University.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Takuya
authors.initials: T
authors.lastname: Katsutani
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Hara
authors.forename: Naomi
authors.initials: N
authors.lastname: Motoyoshi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Itagaki
authors.forename: Fusamichi
authors.initials: F
authors.lastname: Akita
authors.forename: Akifumi
authors.initials: A
authors.lastname: Higashiura
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yamada
authors.forename: Norio
authors.initials: N
authors.lastname: Inokuchi
authors.forename: Mamoru
authors.initials: M
authors.lastname: Suzuki
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D003460:Crystallization; D018360:Crystallography, X-Ray; D004591:Electrophoresis, Polyacrylamide Gel; D018922:HL-60 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D020076:Pleurotus / Q000201:enzymology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D006163:Ribonuclease T1 / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C091184:ribonuclease Po1; D006163:Ribonuclease T1