Conformational dynamics play important roles upon the function of N-acetylglutamate kinase
Conformational dynamics play important roles upon the function of N-acetylglutamate kinase
复制标题
构象动力学对 N-乙酰谷氨酸激酶的功能发挥重要作用
DOI：
10.1007/s00253-017-8237-1
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发表时间：
2017-03
影响因子：
5
通讯作者：
Yang Xiaorong
中科院分区：
文献类型：
--
作者：
Yang Xiaorong
N-乙酰谷氨酸激酶（NAGK）催化N-乙酰谷氨酸的磷酸化。在许多细菌中，NAGK催化是L-精氨酸生物合成途径中从谷氨酸到L-精氨酸的速率控制步骤，并且被L-精氨酸别构抑制。许多数据表明，NAGK的构象动力学对其功能至关重要。构象机理的论证为提高精氨酸的产率提供了一条潜在的途径。由于哺乳动物精氨酸合成途径中缺少NAGK催化步骤，阐明其动力学机制也可为设计新的抗病毒药物提供思路。本文综述了这些动力学过程如何影响NAGKs的活性以及受效应物的控制。X射线晶体学和建模数据表明，在NAGK中，抑制剂和底物结合、催化和产物释放所需的结构元件是高度移动的。可以通过干扰NAGK的柔性来消除精氨酸的抑制和/或阻断精氨酸的合成。氨基酸激酶家族被认为具有一些共同的动力学特征; NAGK的柔性结构元件已经被确定，但动力学和信号传递途径的细节尚未阐明。
N-acetylglutamate kinase (NAGK) catalyzes the phosphorylation of N-acetylglutamate. In many bacteria, NAGK catalysis is the rate controlling step in the L-arginine biosynthesis pathway from glutamate to L-arginine and is allosterically inhibited by L-arginine. Many data show that conformational dynamics of NAGKs are essential for their function. The demonstration of the conformational mechanism provides a potential way to improve the yield of arginine. Due to the lack of NAGK catalysis step in arginine synthesis route of mammals, the elucidation of the dynamic mechanism can also provide a way to design a new antivirus drug. This paper reviews how the dynamics affect the activity of NAGKs and are controlled by the effectors. X-ray crystallography and modeling data have shown that in NAGKs, the structural elements required for inhibitor and substrate binding, catalysis and product release, are highly mobile. It is possible to eliminate the inhibition of the arginine and/or block the synthesis of arginine by disturbing the flexibility of the NAGKs. Amino acid kinase family is thought to share some common dynamic features; the flexible structural elements of NAGKs have been identified, but the details of the dynamics and the signal transfer pathways are yet to be elucidated.
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