Refined 1.7 A X-ray crystallographic structure of P-30 protein, an amphibian ribonuclease with anti-tumor activity.
The X-ray crystallographic structure of P-30 protein (Onconase) has been solved by multiple isomorphous replacement and the structure has been refined at 1.7 A resolution to a conventional R-factor of 0.178. The molecular model comprises all 826 non-hydrogen protein atoms, 96 solvent molecules and a sulfate anion that is bound at the active site. The molecular structure is similar to that of ribonuclease A. The active site cleft is located at the junction of two three-stranded beta-sheets and the N-terminal helix. A sulfate anion is non-covalently bound by Lys9, His10, His97, Phe98 and an intermolecular contact involving Lys55' from a neighboring molecule. The N-terminal pyroglutamyl (Pyr) residue is part of the active site and its O epsilon 1 atom forms a hydrogen bond with the Lys9 N zeta. The previously constructed comparative molecular model of P-30 based on ribonuclease A correctly predicted the overall fold of P-30 and the conformation of its active site residues. The model failed to predict the conformation of Pyr1 and the conformation of the two loops following helix alpha 3 and strand beta 3.
Mosimann
S C
SC
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Ardelt
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W
James
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MN
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004527:Egg Proteins / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D011894:Rana pipiens; D012260:Ribonucleases / Q000737:chemistry*
D000970:Antineoplastic Agents; D004527:Egg Proteins; D012260:Ribonucleases; C058703:ranpirnase