TY - JOUR AU - Pokrovskaya, M.V. AU - Aleksandrova, S.S. AU - Veselovsky, A.V. AU - Zdanov, D.D. AU - Pokrovsky, V.S. AU - Eldarov, M.A. AU - Grishin, D.V. AU - Gladilina, Yu.A. AU - Toropigin, I.Yu. AU - Sokolov, N.N. PY - 2019/02/13 Y2 - 2024/03/29 TI - Physical-Chemical Properties of L-Asparaginase Mutants From Rhodospirillum Rubrum which Showed Antitelomerase Activity JF - Biomedical Chemistry: Research and Methods JA - BIOMED CHEM RM VL - 2 IS - 1 SE - EXPERIMENTAL RESEARCH DO - 10.18097/BMCRM00071 UR - http://bmc-rm.org/index.php/BMCRM/article/view/71 SP - e00071 AB - <p>Rru_A3730 protein is a bacterial <em>Rhodospirillum rubrum</em> 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: RrA<sub>17N, K149E</sub>, RrA<sub>E149R, V150P, F151T</sub>, RrА<sub>17N, E149R, V150P</sub>, RrA<sub>E149R, V150P</sub>, 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<sup>+</sup>, Ca<sup>2+</sup>, Zn<sup>2+</sup>, Cs<sup>+</sup>, Co<sup>2+</sup> in significantly affect the activity of L-asparaginase, while Mn<sup>2+</sup>, Cu<sup>2+</sup>, Fe<sup>3+</sup> ions inhibit it. There was no correlation between antitelomerase (antiproliferative) activity and kinetic properties of mutant forms of L-asparaginase RrA.</p> ER -