Conformational changes in the tryptophan synthase from a hyperthermophile upon α2β2 complex formation:: Crystal structure of the complex
Conformational changes in the tryptophan synthase from a hyperthermophile upon α2β2 complex formation:: Crystal structure of the complex
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DOI：
10.1021/bi050317h
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发表时间：
2005-08-30
期刊：
影响因子：
2.9
通讯作者：
Yutani, K
中科院分区：
文献类型：
--
作者：
Lee, SJ;Ogasahara, K;Yutani, K
用晶体学方法测定了荧光焦球菌双功能色氨酸合成酶(α (2) β(2))复合物的三维结构。这种晶体结构，具有α亚基单体和β(2)亚基二聚体的结构，是第一个在单个色氨酸合成酶亚基结合时发生结构变化的结构集。为了阐明α (2) β(2)配合物形成时α和β(2)亚基各酶活性受到刺激的结构基础，与α (2) β(2)单体和82亚基二聚体的结构进行了详细的构象变化分析。在与酶的催化功能相关的区域，由于络合物的形成而发生的主要构象变化如下。(1) β亚基的结构变化大于cc亚基。(2) α亚基中的A46和L165由于复杂的形成而大量移动，导致更开放的构象有利于底物进入a活性位点。(3) β亚基的主要变化是a亚基产物（吲哚）转移到P活性位点的长通道变宽以及β活性位点的入口打开。(4)由于复合物的形成，α和β亚基构象的变化有助于亚基结合的稳定，这对刺激酶活性至关重要。
The three-dimensional structure of the bifunctional tryptophan synthase (alpha(2)beta(2) complex from Pyrococcus furiosus was determined by crystallographic analysis. This crystal structure, with the structures of an alpha subunit monomer and a beta(2) subunit dimer that have already been reported, is the first structural set in which changes in structure that occur upon the association of the individual tryptophan synthase subunits were observed. To elucidate the structural basis of the stimulation of the enzymatic activity of each of the alpha and beta(2) subunits upon alpha(2)beta(2) complex formation, the conformational changes due to complex formation were analyzed in detail compared with the structures of the a monomer and,82 subunit dimer. The major conformational changes due to complex formation occurred in the region correlated with the catalytic function of the enzyme as follows. (1) Structural changes in the beta subunit were greater than those in the cc subunit. (2) Large movements of A46 and L165 in the alpha subunit due to complex formation caused a more open conformation favoring the entry of the substrate at the a active site. (3) The major changes in the beta subunit were the broadening of a long tunnel through which the a subunit product (indole) is transferred to the P active site and the opening of an entrance at the beta active site. (4) The changes in the conformations of both the alpha and beta subunits due to complex formation contributed to the stabilization of the subunit association, which is critical for the stimulation of the enzymatic activities.