STEREOCHEMICAL ANALYSIS OF RIBOSOMAL TRANSPEPTIDATION - CONFORMATION OF NASCENT PEPTIDE
STEREOCHEMICAL ANALYSIS OF RIBOSOMAL TRANSPEPTIDATION - CONFORMATION OF NASCENT PEPTIDE
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DOI：
10.1016/s0022-2836(86)80006-7
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发表时间：
1986-04-20
影响因子：
5.6
通讯作者：
SPIRIN, AS
中科院分区：
文献类型：
--
作者：
LIM, VI;SPIRIN, AS
核糖体进行的转肽化被认为是一个亲核Sn2取代反应，通过一个四面体中间体。假设所有20个氨基酸残基在被攻击的（供体）和被攻击的（受体）底物中都存在一个立体化学的普遍反应机制。在四面体中间体中，被攻击羰基碳的键周围和相邻键周围的内旋角以及中间体的立体构型都发生了变化。通过使用Corey-Pauling-Koltun模型和允许原子间距离和。+-的“极端极限”的直接计算，分析了所有54种由5个扭转角确定的空间允许的旋转异构体组合。7.学位。键角偏差。只有一种组合，即四面体中间体的一种独特构象，被发现与所有400对可能的反应氨基酸残基在空间上相容，同时能够切割成一个平面反式肽基。扭转角。和.psi。这种普遍存在的中间产物及其裂解产生的肽产物与α -螺旋中的产物相似。这表明核糖体产生。α。-螺旋构象在新生肽的c端。
Transpeptidation performed by the ribosome is considered as a nucleophilic Sn2 substitution reaction, passing through a tetrahedral intermediate. A stereochemically universal mechanism of the reaction is assumed to exist for all 20 amino acid residues, both in the attacked (donor) and in the attacking (acceptor) substrates. The angles of internal rotation around the bonds of the attacked carbonyl carbon and around the neighboring bonds in the tetrahedral intermediate, as well as the stereoconfiguration of the intermediate, have been varied. All 54 combinations of the sterically allowed rotational isomers determined by the five torsional angles have been analyzed by using Corey-Pauling-Koltun models and by direct calculations permitting the "extreme limits" in interatomic distances and .+-. 7.degree. deviations in bond angles. Only one combination, i.e. one unique conformation of the tetrahedral intermediate, is found to be sterically compatible with all 400 possible pairs of the reacting amino acid residues and at the same time to be capable of cleaving into a planar trans-peptide group. The torsion angles .rho. and .psi. of this universally allowed intermediate and the peptide product resulting from its cleavage are similar to those in an .alpha.-helix. It is suggested that the ribosome generates the .alpha.-helical conformation at the C-end of the nascent peptide.