The interactions of the classic phytohormones gibberellic acid (gibberellin A₃, GA₃) and abscisic acid (dormin, ABA), which antagonistically regulate several developmental processes and stress responses in higher plants, with human placental glutathione S-transferase P1-1 (hpGSTP1-1), an enzyme that plays a role in endo- or xenobiotic detoxification and regulation of cell survival and apoptosis, were investigated. The inhibitory potencies of ABA and GA₃ against hpGSTP1, as well as the types of inhibition and the kinetic parameters, were determined by making use of both enzyme kinetic graphs and SPSS nonlinear regression models. The structural basis for the interaction between hpGSTP1-1 and phytohormones was predicted with the aid of molecular docking simulations. The IC₅₀ values of ABA and GA₃ were 5.3 and 5.0 mM, respectively. Both phytohormones inhibited hpGSTP1-1 in competitive manner with respect to the cosubstrates GSH and CDNB. When ABA was the inhibitor at [CDNB]_f–[GSH]_v and at [GSH]_f–[CDNB]_v, V_m, K_m, and K_i values were statistically estimated to be 205 ± 16 μmol/min-mg protein, 1.32 ± 0.18 mM, 1.95 ± 0.25 mM and 175 ± 6 μmol/min-mg protein, 0.85 ± 0.06 mM, 1.85 ± 0.16 mM, respectively. On the other hand, the kinetic parameters V_m, K_m, and K_i obtained with GA₃ at [CDNB]_f–[GSH]_v and at [GSH]_f–[CDNB]_v were found to be 303 ± 14 μmol/min-mg protein, 1.77 ± 0.13 mM, 3.38 ± 0.26 mM and 249 ± 7 μmol/min-mg protein, 1.43 ± 0.07 mM, 2.89 ± 0.19 mM, respectively. Both phytohormones had the potential to engage in hydrogen-bonding and electrostatic interactions with the key residues that line the G- and H-sites of the enzyme's catalytic center. Inhibitory actions of ABA/GA₃ on hpGSTP1-1 may guide medicinal chemists through the structure-based design of novel antineoplastic agents. It should be noted, however, that the same interactions may also render fetuses vulnerable to the potentially toxic effects of xenobiotics and noxious endobiotics.

中文翻译：

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脱落酸和赤霉酸抑制人胎盘谷胱甘肽 S-转移酶 P1-1 的机制见解：综合实验和计算研究

经典植物激素赤霉酸 (gibberellin A ₃ , GA _{3 ) 和脱落酸 (dormin, ABA) 与人胎盘谷胱甘肽}S -转移酶 P1-1 ( hp ) 的相互作用，拮抗地调节高等植物的几个发育过程和应激反应GSTP1-1）是一种在内生或外生物质解毒以及细胞存活和凋亡调节中发挥作用的酶。利用酶动力学图和SPSS非线性回归模型确定ABA和GA ₃对hp GSTP1的抑制效力以及抑制类型和动力学参数。借助分子对接模拟，预测了hp GSTP1-1 与植物激素之间相互作用的结构基础。ABA和GA ₃的IC _{50值分别为5.3}和5.0 mM。两种植物激素均以与共底物 GSH 和 CDNB 竞争的方式抑制hp GSTP1-1。当 ABA 为 [CDNB] _f –[GSH] _v和 [GSH] _f –[CDNB] _v的抑制剂时，V _m、K _m和K _i值统计估计为 205 ± 16 μmol/min-mg蛋白质，分别为 1.32 ± 0.18 mM、1.95 ± 0.25 mM 和 175 ± 6 μmol/min-mg 蛋白质，分别为 0.85 ± 0.06 mM、1.85 ± 0.16 mM。另一方面， GA ₃在 [CDNB] _f –[GSH] _v和 [GSH] _f –[CDNB] _v处获得的动力学参数V _m、K _m和K _i为 303 ± 14 μmol /min-mg 蛋白质，分别为 1.77 ± 0.13 mM、3.38 ± 0.26 mM 和 249 ± 7 μmol/min-mg 蛋白质，1.43 ± 0.07 mM、2.89 ± 0.19 mM。两种植物激素都有可能与酶催化中心 G 和 H 位点上的关键残基发生氢键和静电相互作用。_{ABA/GA 3}对hp GSTP1-1的抑制作用可以指导药物化学家基于结构设计新型抗肿瘤药物。然而，应该指出的是，同样的相互作用也可能使胎儿容易受到外源物质和有毒内生物质潜在毒性作用的影响。