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Molecules 2014, 19(2), 1828-1842; doi:10.3390/molecules19021828

Theoretical Study on the Allosteric Regulation of an Oligomeric Protease from Pyrococcus horikoshii by Cl Ion

1,*  and 1,*
1 Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun 130023, China 2 College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China 3 Norman Bethune College of Medicine, Jilin University, Changchun 130021, China These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 19 December 2013 / Revised: 23 January 2014 / Accepted: 27 January 2014 / Published: 7 February 2014
(This article belongs to the Special Issue In-Silico Drug Design and In-Silico Screening)
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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.
Keywords: oligomeric protease; allosteric regulation; molecular dynamics simulation oligomeric protease; allosteric regulation; molecular dynamics simulation
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Zhan, D.; Sun, J.; Feng, Y.; Han, W. Theoretical Study on the Allosteric Regulation of an Oligomeric Protease from Pyrococcus horikoshii by Cl Ion. Molecules 2014, 19, 1828-1842.

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