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A synapomorphic disulfide bond is critical for the conformational stability and cytotoxicity of an amphibian ribonuclease
Author(s) -
Leland Peter A.,
Staniszewski Kristine E.,
Kim Byung-Moon,
Raines Ronald T.
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01804-4
Subject(s) - amphibian , ribonuclease , cytotoxicity , chemistry , disulfide bond , rnase p , synapomorphy , biophysics , biochemistry , biology , rna , ecology , phylogenetic tree , in vitro , gene , clade
Onconase ® (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.