Tworowski Dmitry, Feldman Anna V, Safro Mark G
Department of Structural Biology, Weizmann Institute of Science, 76100 Rehovot, Israel.
J Mol Biol. 2005 Jul 29;350(5):866-82. doi: 10.1016/j.jmb.2005.05.051.
In the first stage of a diffusion-controlled enzymatic reaction, aminoacyl-tRNA synthetases (aaRSs) interact with cognate tRNAs forming non-specific encounters. The aaRSs catalyzing the same overall aminoacylation reaction vary greatly in subunit organization, structural domain composition and amino acid sequence. The diffusional association of aaRS and tRNA was found to be governed by long-range electrostatic interactions when the homogeneous negative potential of tRNA fits to the patches of positive potential produced by aaRS; one patch for each tRNA substrate molecule. Considering aaRS as a molecule with anisotropic reactivity and on the basis of continuum electrostatics and Smoluchowski's theory, the reaction conditions for tRNA-aaRS diffusional encounters were formulated. The domains, categorized as enzymatically relevant, appeared to be non-essential for field sculpturing at long distances. On the other hand, a set of complementary domains exerts primary control on the aaRS isopotential surface formation. Subdividing the aaRS charged residues into native, conservative and non-conservative subsets, we evaluated the contribution of each group to long-range electrostatic potential. Surprisingly, the electrostatic potential landscapes generated by native and non-conservative subsets are fairly similar, thus suggesting the non-conservative subset is developed specifically for efficient tRNA attraction.
在扩散控制的酶促反应的第一阶段，氨酰 - tRNA合成酶（aaRSs）与同源tRNA相互作用形成非特异性相遇。催化相同总体氨酰化反应的aaRSs在亚基组织、结构域组成和氨基酸序列上有很大差异。当tRNA的均匀负电位与aaRS产生的正电位区域相匹配时，发现aaRS与tRNA的扩散结合受长程静电相互作用支配；每个tRNA底物分子有一个区域。将aaRS视为具有各向异性反应性的分子，并基于连续介质静电学和斯莫卢霍夫斯基理论，制定了tRNA - aaRS扩散相遇的反应条件。归类为与酶促相关的结构域，似乎对远距离的场塑造并非必不可少。另一方面，一组互补结构域对aaRS等电位面的形成起主要控制作用。将aaRS的带电残基细分为天然、保守和非保守子集，我们评估了每组对长程静电势的贡献。令人惊讶的是，天然和非保守子集产生的静电势景观相当相似，因此表明非保守子集是专门为有效吸引tRNA而形成的。
