Zhang H, Vrang L, Bäckbro K, Unge T, Noréen R, Oberg B
Medivir AB, Huddinge, Sweden.
Antiviral Res. 1994 May;24(1):43-57. doi: 10.1016/0166-3542(94)90051-5.
Two mutants of HIV-1 reverse transcriptase (RT), Tyr-188-->His and Glu-138-->Arg have been prepared and their catalytic properties and sensitivities to inhibitors studied. As compared to wild type RT, a reduction in catalytic efficiency and turn over number was observed, especially for the Tyr-188-->His mutant. The non-nucleoside inhibitors nevirapine, L-697,661 and 9-Cl-TIBO caused a mixed type of inhibition of RT (Arg-138) with respect to substrate, and with the exception of a non-competitive inhibition by nevirapine, also a mixed type of inhibition of RT (His-188). Foscarnet (PFA) caused a non-competitive type of inhibition of RT (Arg-138) and a mixed inhibition of RT (His-188). The inhibition by ddG-TP was competitive with both mutant RTs. Inhibition by nevirapine gave IC50 values of 0.15, 0.23 and 0.72 microM; by 9-Cl-TIBO of 0.20, 2.50 and 10.3 microM; by L-697,661 of 0.064, 0.28 and 0.60 microM; by ddGTP of 0.13, 0.14 and 0.02 microM; by PFA of 17.0, 48.0 and 15.0 microM for RT wt, RT (Arg-138) and RT (His-188), respectively.
已制备出两种HIV-1逆转录酶（RT）突变体，即Tyr-188→His和Glu-138→Arg，并对其催化特性及对抑制剂的敏感性进行了研究。与野生型RT相比，观察到催化效率和周转数有所降低，尤其是Tyr-188→His突变体。非核苷类抑制剂奈韦拉平、L-697,661和9-Cl-TIBO对底物而言对RT（Arg-138）产生混合型抑制，除奈韦拉平的非竞争性抑制外，对RT（His-188）也产生混合型抑制。膦甲酸钠（PFA）对RT（Arg-138）产生非竞争性抑制，对RT（His-188）产生混合型抑制。ddG-TP对两种突变型RT均产生竞争性抑制。奈韦拉平的抑制作用使野生型RT、RT（Arg-138）和RT（His-188）的IC50值分别为0.15、0.23和0.72微摩尔；9-Cl-TIBO的分别为0.20、2.50和10.3微摩尔；L-697,661的分别为0.064、0.28和0.60微摩尔；ddGTP的分别为0.13、0.14和0.02微摩尔；PFA的分别为17.0、48.0和1
