Physical-Chemical Properties of L-Asparaginase Mutants From Rhodospirillum Rubrum which Showed Antitelomerase Activity

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M.V. Pokrovskaya
S.S. Aleksandrova
A.V. Veselovsky
D.D. Zdanov
V.S. Pokrovsky
M.A. Eldarov
D.V. Grishin
Yu.A. Gladilina
I.Yu. Toropigin
N.N. Sokolov


Rru_A3730 protein is a bacterial Rhodospirillum rubrum L-asparaginase (RrA), which is known by its anticancer activity. RrA variants with point amino acid substitutions in the region of 150 amino acids residues: RrA17N, K149E, RrAE149R, V150P, F151T, RrА17N, E149R, V150P, RrAE149R, V150P, showed antiproliferative properties, and also by their ability to suppress telomerase activity. This work is devoted to comparison of physical-chemical and catalytic properties of these mutant forms of RrA. It is shown that pH optimum is in the alkaline zone (8.5 – 9.3); L-glutaminase and D-asparaginase activity is respectively not more than 0.1% and 1.6% of L-asparaginase for all studied variants of RrA. The presence of the N17-terminal amino acid sequence MASMTGGQMGRGSSRQ of the capsid protein of bacteriophage T7 in the RrA structure leads to an increase in the thermal stability of mutant RrA analogues (from 50°C to 56°C) and their resistance to denaturation in the presence of 3 – 4 M urea. It is of Metal ions exhibit multidirectional effects on L-asparaginase activity of RrA. K+, Ca2+, Zn2+, Cs+, Co2+ in significantly affect the activity of L-asparaginase, while Mn2+, Cu2+, Fe3+ ions inhibit it. There was no correlation between antitelomerase (antiproliferative) activity and kinetic properties of mutant forms of L-asparaginase RrA.

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Pokrovskaya, M., Aleksandrova, S., Veselovsky, A., Zdanov, D., Pokrovsky, V., Eldarov, M., Grishin, D., Gladilina, Y., Toropigin, I., & Sokolov, N. (2019). Physical-Chemical Properties of L-Asparaginase Mutants From Rhodospirillum Rubrum which Showed Antitelomerase Activity. Biomedical Chemistry: Research and Methods, 2(1), e00071.


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