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首页> 外文期刊>Journal of the Indian Chemical Society >Computational analysis of the structure and stability of the tetrahedral intermediate in the peptide bond formation reaction in peptidyl transferase center
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Computational analysis of the structure and stability of the tetrahedral intermediate in the peptide bond formation reaction in peptidyl transferase center

机译：肽基转移酶中心肽键形成反应中四面体中间体的结构和稳定性的计算分析

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摘要

Peptide synthesis is an important biological reaction. Both concerted and stepwise mechanisms are proposed for the peptide synthesis in ribosome. The stepwise mechanism takes place through a tetrahedral intermediate. We analyzed the geometry, chirality and stabilizing factors of the intermediate using a combined quantum mechanical/ semiempirical method based on a model of crystal structure. The comparison of the optimized geometry of the intermediate and transition state analog (DCSN) shows that in case of ribosomal peptide synthesis the intermediate should be tetrahedral with S-chirality. The chiral specificity of the intermediate arises from the relative position of the A-site substrate and the P-site substrate. The present computational study conclusively shows that the geometry of the carbonyl carbon atom of P-site amino acid is changed from a planer state (reactant) to another planer state (product) via a tetrahedral intermediate during the peptide bond formation in the ribosome. The tetrahedral intermediate is chiral and has S-chirality. The specificity of chiral structure of the intermediate arises from the relative position of the A-site substrate and the P-site substrate. The generation of the other isomer of the tetrahedral intermediate (R isomer) is impossible during the peptide biosynthesis in the ribosome. As the architecture of the PTC is such that P-site and A-site substrates are enclosed in specific locations, other positions of the substrates are impossible. Consequently the nucleo-philic attack by the cc-amino group of A-site substrate from the two faces of the carbonyl carbon atom of P-site substrate is impossible. As a result only one isomer of the tetrahedral intermediate is possible during the ribosomal peptide synthesis which is stabilized via intra as well as intermolecular hydrogen bonding interactions. The U2620 plays an important role in the stabilization of the geometry of the intermediate. This study is the first computational analysis of the structure and stabilization of the tetrahedral intermediate during the stepwise pathway of peptide synthesis.
机译：肽合成是重要的生物反应。对于核糖体中的肽合成，提出了协同和逐步的机制。逐步机理通过四面体中间体发生。我们使用了基于晶体结构模型的组合量子力学/半经验方法，分析了中间体的几何形状，手性和稳定因子。对中间体和过渡态类似物（DCSN）的最佳几何结构的比较表明，在合成核糖体肽的情况下，中间体应为具有S手性的四面体。中间体的手性特异性来自A位底物和P位底物的相对位置。本计算研究最终表明，在核糖体中形成肽键的过程中，P位氨基酸的羰基碳原子的几何形状通过四面体中间体从平面态（反应物）变为另一平面态（产物）。四面体中间体是手性的并且具有S-手性。中间体的手性结构的特异性源自A位底物和P位底物的相对位置。在核糖体中肽生物合成过程中，不可能生成四面体中间体的其他异构体（R异构体）。由于PTC的体系结构使得P位置和A位置的基板被封闭在特定的位置，因此基板的其他位置是不可能的。因此，不可能从P位底物的羰基碳原子的两个表面通过A位底物的cc-氨基进行亲核攻击。结果，在核糖体肽合成过程中只有四面体中间体的一种异构体是可能的，该异构体通过内部以及分子间的氢键键合作用得以稳定。 U2620在稳定中间体几何形状方面起着重要作用。这项研究是在肽合成的逐步途径中对四面体中间体的结构和稳定性的首次计算分析。

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