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Vol 49(2015) N 6 p. 933-938; DOI 10.1134/S0026893315060199  V.A. Mitkevich1*, C.N. Pace2, A. Koschinski3, A.A. Makarov1, O.N. Ilinskaya4 Cytotoxicity mechanism of the RNase Sa cationic mutants involves inhibition of potassium current through Ca2+-activated channels 1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia;2Texas A&M University, College Station, Texas, 77843 United States 3Medical Science Division, University of Oxford, Oxford OX3 9DU, United Kingdom 4Department of Microbiology, Kazan Federal Volga-Region University, Kazan, 420008 Russia *mitkevich@gmail.com Received - 2015-04-16; Accepted - 2015-06-15 Bacterial ribonucleases (RNases) are considered to be potential anticancer agents. One of most important determinants of RNase cytotoxicity is the net charge of the molecule. In this work, a set of mutants of the RNase from Streptomyces aureofaciens (RNase Sa), differing in the net charge of the protein molecules (from -7 to +6) and localization of additional positive charge at the N- or C-terminus of the molecule were used to investigate the inhibition of cell growth. It has been found that RNase mutants with increased cationicity most effectively inhibit the proliferation of HEKhSK4 cells. An additional positive charge at C-terminus of the molecule also increases the cytotoxic properties of RNases. It has been shown that RNase cytotoxicity correlated with the level of inhibition of K+ current in cells. net charge of proteins, cytotoxicity, Ca2+-activated potassium channels, cationic RNases |
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