Induced fit on sugar binding activates ribokinase
Induced fit on sugar binding activates ribokinase
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DOI：
10.1006/jmbi.1999.2938
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发表时间：
1999-07-30
影响因子：
5.6
通讯作者：
Mowbray, SL
中科院分区：
文献类型：
--
作者：
Sigrell, JA;Cameron, AD;Mowbray, SL
作为代谢的第一步，核糖激酶在O5*处磷酸化核糖。大肠杆菌核糖激酶的原始x射线结构为核糖和ADP三元配合物。这里介绍了载脂蛋白酶的结构，以及核糖结合状态和四种新的三元配合物形式。综上所述，这些结构表明大大小小的构象变化在该激酶的功能中起着关键作用。最初开放的载脂蛋白形式允许核糖底物进入。在核糖结合后，观察到活性位点Lid呈封闭构象，糖被困在其下。这种关闭和蛋白质的相关变化似乎有助于核糖激酶识别共底物ATP作为下一步。核苷酸的结合会对酶的结构带来进一步的、不那么剧烈的调整。在磷酸化转移反应中，几乎肯定需要额外的小运动。证据表明，在三元配合物中，某些类型的盖子运动是允许的，这可能对过渡态的产生和分解至关重要。类似的事件可能发生在其他相关碳水化合物激酶的催化过程中，包括腺苷激酶。(C) 1999学术出版社。
The enzyme ribokinase phosphorylates ribose at O5* as the first step in its metabolism. The original X-ray structure of Escherichia coli ribokinase represented the ternary complex including ribose and ADP. Structures are presented here for the apo enzyme, as well as the ribose-bound state and four new ternary complex forms. Combined, the structures suggest that large and small conformational changes play critical roles in the function of this kinase. An initially open apo form can allow entry of the ribose substrate. After ribose binding, the active site Lid is observed in a closed conformation, with the sugar trapped underneath. This closure and associated changes in the protein appear to assist ribokinase in recognition of the co-substrate ATP as the next step. Binding of the nucleotide brings about further, less dramatic adjustments in the enzyme structure. Additional small movements are almost certainly required during the phosphoryltransfer reaction. Evidence is presented that some types of movements of the lid are allowed in the ternary complex, which may be critical to the creation and breakdown of the transition state. Similar events are likely to take place during catalysis by other related carbohydrate kinases, including adenosine kinase. (C) 1999 Academic Press.