Sarkar P, Stringer E A, Maitra U
Proc Natl Acad Sci U S A. 1974 Dec;71(12):4986-90. doi: 10.1073/pnas.71.12.4986.
Thiostrepton, a peptide antibiotic, inhibits the GTP-dependent 70S initiation complex formation (as measured by binding of fMet-tRNA to ribosomes and concomitant hydrolysis of GTP) only when initiation factor 1 is present to permit catalytic recycling of initiation factor 2 in the initiation reaction. When initiation factor 1 is absent, the binding of fMet-tRNA and GTP hydrolysis occur stoichiometrically with respect to initiation factor 2, and thiostrepton has no effect on either reaction under these conditions. Detailed analysis of this inhibition process shows that thiostrepton prevents catalytic recycling of initiation factor 2 by blocking the action of initiation factor 1, which is required for the dissociation of initiation factor 2 from the 70S initiation complex. This dissociation is necessary for the catalytic reutilization of initiation factor 2 in the initiation reaction. The antibiotic does not directly inhibit GTP hydrolysis per se in initiation. The inhibition of fMet-tRNA binding to ribosomes by thiostrepton is also dependent on the concentration of GTP; the inhibition is most pronounced at low concentrations of GTP, but at a high molar ratio of GTP to thiostrepton, the inhibition is completely abolished.
硫链丝菌素是一种肽类抗生素，仅当起始因子1存在以允许起始因子2在起始反应中进行催化循环时，它才会抑制依赖GTP的70S起始复合物的形成（通过甲酰甲硫氨酸 - tRNA与核糖体的结合以及伴随的GTP水解来测量）。当起始因子1不存在时，甲酰甲硫氨酸 - tRNA的结合和GTP水解相对于起始因子2以化学计量方式发生，并且在这些条件下硫链丝菌素对这两个反应均无影响。对这种抑制过程的详细分析表明，硫链丝菌素通过阻断起始因子1的作用来阻止起始因子2的催化循环，而起始因子1是起始因子2从70S起始复合物解离所必需的。这种解离对于起始因子2在起始反应中的催化再利用是必要的。该抗生素本身并不直接抑制起始过程中的GTP水解。硫链丝菌素对甲酰甲硫氨酸 - tRNA与核糖体结合的抑制也取决于GTP的浓度；在低浓度GTP时抑制作用最为明显，但在GTP与硫链丝菌素的高摩尔比下，抑制作用完全消除。
