The active and stable mutant forms of short chain cytoplasmic L-asparaginase type I of Rhodospirillum rubrum (RrA): RrA+N17, D60K, F61L, RrA+N17, A64V, E67K, RrA+N17, E149R, V150P, RrAE149R, V150P and RrAE149R, V150P, F151T were obtained by the method of site-directed mutagenesis. It is established that variants RrA-N17, E149R, V150P, F151T and RrАE149R, V150P are capable to reduce an expression hTERT subunit of telomerase and, hence, activity of telomeres in Jurkat cells, but not in cellular lysates. During too time, L-asparaginasеs of Escherichia coli, Erwinia carotovora and Wolinella succinogenes, mutant forms RrА+N17, D60K, F61L and RrА+N17, A64V, E67K do not suppress of telomerase activity. The assumption of existence in structure RrA of areas (amino acids residues in the position 146-164, 1-17, 60-67) which are responsible for suppression of telomerase activity is made. The received results show that antineoplastic activity of some variants RrA is connected both with reduction of concentration of free L-asparagine, and with expression suppression of hTERT telomerase subunit, that opens new prospects for antineoplastic therapy.
Keywords: L-asparaginase Rhodospirillum rubrum, antineoplastic effect of L-asparaginase, a site-directed mutagenesis, telomerase, hTERT subunit of telomerase
Pokrovskaya M.V. et al. Suppression of telomerase activity leukemic cells by mutant forms of Rhodospirillum rubrum L-asparaginase // Biomeditsinskaya khimiya. - 2017. - V. 63. -N 1. - P. 62-74.
Pokrovskaya M.V. et al., "Suppression of telomerase activity leukemic cells by mutant forms of Rhodospirillum rubrum L-asparaginase." Biomeditsinskaya khimiya 63.1 (2017): 62-74.
Pokrovskaya, M. V., Zhdanov, D. D., Eldarov, M. A., Aleksandrova, S. S., Veselovskiy, A. V., Pokrovskiy, V. S., Grishin, D. V., Gladilina, Ju. A., Sokolov, N. N. (2017). Suppression of telomerase activity leukemic cells by mutant forms of Rhodospirillum rubrum L-asparaginase. Biomeditsinskaya khimiya, 63(1), 62-74.
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