Yang Xiaorong
Guangdong Key Laboratory of Fermentation and Enzyme Engineering, School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, 510006, People's Republic of China.
Guangdong Research Center of Industrial Enzyme and Green Manufacturing Technology, School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, 510006, People's Republic of China.
Appl Microbiol Biotechnol. 2017 May;101(9):3485-3492. doi: 10.1007/s00253-017-8237-1. Epub 2017 Mar 24.
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.
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催化是从谷氨酸到L-精氨酸的L-精氨酸生物合成途径中的速率控制步骤,并受到L-精氨酸的变构抑制。许多数据表明,NAGK的构象动力学对其功能至关重要。构象机制的证明为提高精氨酸产量提供了一条潜在途径。由于哺乳动物精氨酸合成途径中缺乏NAGK催化步骤,阐明动力学机制也可为设计新型抗病毒药物提供一条途径。本文综述了动力学如何影响NAGK的活性以及如何受效应物控制。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具有高度的流动性。通过干扰NAGK的灵活性,有可能消除精氨酸的抑制作用和/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;已经确定了NAGK的柔性结构元件,但动力学细节和信号转导途径尚待阐明。