Conversion of the free energy of NTP hydrolysis efficiently into mechanical work and/or information by transducing enzymes sustains living systems far from equilibrium, and so has been of interest for many decades. Detailed molecular mechanisms, however, remain puzzling and incomplete. We previously reported that catalysis of tryptophan activation by tryptophanyl-tRNA synthetase, TrpRS, requires relative domain motion to re-position the catalytic Mg2+ ion, noting the analogy between that conditional hydrolysis of ATP and the escapement mechanism of a mechanical clock. The escapement allows the time-keeping mechanism to advance discretely, one gear at a time, if and only if the pendulum swings, thereby converting energy from the weight driving the pendulum into rotation of the hands. Coupling of catalysis to domain motion, however, mimics only half of the escapement mechanism, suggesting that domain motion may also be reciprocally coupled to catalysis, completing the escapement metaphor. Computational studies of the free energy surface restraining the domain motion later confirmed that reciprocal coupling: the catalytic domain motion is thermodynamically unfavorable unless the PPi product is released from the active site. These two conditional phenomena-demonstrated together only for the TrpRS mechanism-function as reciprocally-coupled gates. As we and others have noted, such an escapement mechanism is essential to the efficient transduction of NTP hydrolysis free energy into other useful forms of mechanical or chemical work and/or information. Some implementation of both gating mechanisms-catalysis by domain motion and domain motion by catalysis-will thus likely be found in many other systems.

中文翻译：

---

擒纵机构：通过相互耦合的门控进行有效的自由能转换。

通过转导酶将 NTP 水解的自由能有效地转化为机械功和/或信息，使生命系统远离平衡，因此几十年来一直受到关注。然而，详细的分子机制仍然令人费解和不完整。我们之前报道过色氨酸-tRNA 合成酶 TrpRS 对色氨酸活化的催化需要相对域运动来重新定位催化 Mg2+ 离子，注意到 ATP 的条件水解与机械钟的擒纵机制之间的类比。当且仅当摆锤摆动时，擒纵机构允许计时机构一次一个齿轮离散地推进，从而将驱动摆锤的重量的能量转化为指针的旋转。然而，催化与域运动的耦合，仅模仿了擒纵机构的一半，这表明域运动也可能与催化相互耦合，从而完成了擒纵隐喻。限制域运动的自由能表面的计算研究后来证实了相互耦合：催化域运动在热力学上是不利的，除非PPi产物从活性位点释放。这两种条件现象——仅针对 TrpRS 机制一起展示——作为相互耦合的门。正如我们和其他人所指出的那样，这种擒纵机制对于将 NTP 水解自由能有效地转化为其他有用形式的机械或化学功和/或信息至关重要。