Mechanism of phosphoryl transfer catalyzed by shikimate kinase from Mycobacterium tuberculosis
Mechanism of phosphoryl transfer catalyzed by shikimate kinase from Mycobacterium tuberculosis
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DOI：
10.1016/j.jmb.2006.09.001
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发表时间：
2006-12-01
影响因子：
5.6
通讯作者：
Bartunik, Hans D.
中科院分区：
文献类型：
--
作者：
Hartmann, Marcus D.;Bourenkov, Gleb P.;Bartunik, Hans D.
基于一系列对应于酶促反应中各个步骤的高分辨率晶体结构，研究了结核分枝杆菌莽草酸激酶催化功能的结构机制。在结晶环境中，研究了莽草酸和ATP催化转化为产物莽草酸-3-磷酸和ADP，然后释放ADP的过程。基于反应开始之前和催化步骤之后的结构状态的比较，我们推导出过渡态的结构模型，该模型表明磷酰基转移通过在线关联机制进行反转。莽草酸和核苷酸的随机顺序结合与结构域运动有关。我们确定了一种协同机制，通过该机制，第一底物的结合可以增强对第二底物的亲和力。(c)2006爱思唯尔有限公司保留所有权利。
The structural mechanism of the catalytic functioning of shikimate kinase from Mycobacterium tuberculosis was investigated on the basis of a series of high-resolution crystal structures corresponding to individual steps in the enzymatic reaction. The catalytic turnover of shikimate and ATP into the products shikimate-3-phosphate and ADP, followed by release of ADP, was studied in the crystalline environment. Based on a comparison of the structural states before initiation of the reaction and immediately after the catalytic step, we derived a structural model of the transition state that suggests that phosphoryl transfer proceeds with inversion by an in-line associative mechanism. The random sequential binding of shikimate and nucleotides is associated with domain movements. We identified a synergic mechanism by which binding of the first substrate may enhance the affinity for the second substrate. (c) 2006 Elsevier Ltd. All rights reserved.