Theoretical Study on the Allosteric Regulation of an Oligomeric Protease from Pyrococcus horikoshii by Cl-Ion
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.
oligomeric protease allosteric regulation molecular dynamics simulation
Dongling Zhan Jiao Sun Yan Feng Weiwei Han
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education,Jilin University, C Norman Bethune College of Medicine, Jilin University, Changchun 130021, China Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education,Jilin University, C
国内会议
苏州
英文
497-511
2014-10-26（万方平台首次上网日期，不代表论文的发表时间）