A synapomorphic disulfide bond is critical for the conformational stability and cytotoxicity of an amphibian ribonuclease.
Onconase((R)) (ONC) is a homolog of ribonuclease A (RNase A) that has unusually high conformational stability and is toxic to human cancer cells in vitro and in vivo. ONC and its amphibian homologs have a C-terminal disulfide bond, which is absent in RNase A. Replacing this cystine with a pair of alanine residues greatly decreases the conformational stability of ONC. In addition, the C87A/C104A variant is 10-fold less toxic to human leukemia cells. These data indicate that the synapomorphic disulfide bond of ONC is an important determinant of its cytotoxicity.
Leland
P A
PA
Department of Biochemistry, University of Wisconsin-Madison, 420 Henry Mall, Madison, WI 53706-1569, USA.
Staniszewski
K E
KE
Kim
B
B
Raines
R T
RT
D002942:Circular Dichroism; D004220:Disulfides / Q000737:chemistry*; D006801:Humans; D006868:Hydrolysis; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D012260:Ribonucleases / Q000737:chemistry* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004220:Disulfides; D011994:Recombinant Proteins; D012260:Ribonucleases