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New muteins of RNase A with enhanced antitumor action
Author(s) -
Cafaro Valeria,
Bracale Aurora,
Di Maro Antimo,
Sorrentino Salvatore,
D'Alessio Giuseppe,
Di Donato Alberto
Publication year - 1998
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(98)01221-6
Subject(s) - rnase p , s tag , pancreatic ribonuclease , bovine pancreatic ribonuclease , ribonuclease , chemistry , mutant , biochemistry , mutagenesis , rnase h , cysteine , angiogenin , rnase ph , glycine , site directed mutagenesis , rnase mrp , amino acid , microbiology and biotechnology , protein subunit , enzyme , biology , rna , gene , genetics , angiogenesis
Monomeric bovine pancreatic RNase A has been transformed into a dimeric ribonuclease with antitumor activity (Di Donato, A., Cafaro, V. and D'Alessio, G. (1994) J. Biol. Chem. 269, 17394–17396). This was accomplished by replacing the residues located in the RNase chain at positions 19, 28, 31, and 32, with proline, leucine, and two cysteine residues, respectively, i.e. those present at identical positions in the subunit of bovine seminal RNase, a dimeric RNase of the pancreatic‐type superfamily, endowed with a powerful antitumor action. However, as an antitumor agent this mutant dimeric RNase A is not as powerful as seminal RNase. We report here site‐directed mutagenesis experiments which have led to the identification of two other amino acid residues, glycine 38 and 111, whose substitution in the polypeptide chain of the first generation dimeric mutant of RNase A, is capable of conferring to the mutein the full cytotoxic activity characteristic of native seminal RNase.