Zhan Dongling, Sun Jiao, Feng Yan, Han Weiwei
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun 130023, China.
Norman Bethune College of Medicine, Jilin University, Changchun 130021, China.
Molecules. 2014 Feb 7;19(2):1828-42. doi: 10.3390/molecules19021828.
The thermophilic intracellular protease (PH1704) from Pyrococcus horikoshii that functions as an oligomer (hexamer or higher forms) has proteolytic activity and remarkable stability. PH1704 is classified as a member of the C56 family of peptidases. This study is the first to observe that the use of Cl- as an allosteric inhibitor causes appreciable changes in the catalytic activity of the protease. Theoretical methods were used for further study. Quantum mechanical calculations indicated the binding mode of Cl- with Arg113. A molecular dynamics simulation explained how Cl- stabilized distinct contact species and how it controls the enzyme activity. The new structural insights obtained from this study are expected to stimulate further biochemical studies on the structures and mechanisms of allosteric proteases. It is clear that the discovery of new allosteric sites of the C56 family of peptidases may generate opportunities for pharmaceutical development and increases our understanding of the basic biological processes of this peptidase family.
来自嗜热栖热菌的嗜热细胞内蛋白酶（PH1704）以寡聚体（六聚体或更高形式）发挥作用，具有蛋白水解活性和显著的稳定性。PH1704被归类为肽酶C56家族的成员。本研究首次观察到，使用Cl-作为变构抑制剂会导致蛋白酶的催化活性发生明显变化。采用理论方法进行进一步研究。量子力学计算表明了Cl-与Arg113的结合模式。分子动力学模拟解释了Cl-如何稳定不同的接触物种以及如何控制酶活性。预计本研究获得的新结构见解将刺激对变构蛋白酶的结构和机制进行进一步的生化研究。显然，肽酶C56家族新变构位点的发现可能为药物开发创造机会，并增进我们对该肽酶家族基本生物学过程的理解。
