0435268 - ÚVGZ 2015 RIV CZ eng J - Journal Article
Pandey, Saurabh Kumar - Řeha, David - Zayats, Vasilina - Melicherčík, Milan - Carey, J. - Ettrich, Rüdiger
Binding-competent states for L-arginine in E. coli arginine repressor apoprotein.
Journal of Molecular Modeling. Roč. 20, č. 7 (2014), s. 2330. ISSN 1610-2940. E-ISSN 0948-5023
Institutional support: RVO:67179843
Keywords : allostery * ArgRC * conformational dynamics * principal components analysis * salt bridges * temporal evolution of conformers
Subject RIV: CE - Biochemistry
Impact factor: 1.736, year: 2014
DOI: https://doi.org/10.1007/s00894-014-2330-5

Arginine repressor of E. coli is a multifunctional hexameric protein that provides feedback regulation of arginine metabolism upon activation by the negatively cooperative binding of L-arginine. Interpretation of this complex system requires an understanding of the protein's conformational landscape. The similar to 50 kDa hexameric C-terminal domain was studied by 100 ns molecular dynamics simulations in the presence and absence of the six L-arg ligands that bind at the trimer-trimer interface. A rotational shift between trimers followed by rotational oscillation occurs in the production phase of the simulations only when L-arg is absent. Analysis of the system reveals that the degree of rotation is correlated with the number of hydrogen bonds across the trimer interface. The trajectory presents frames with one or more apparently open binding sites into which one L-arg could be docked successfully in three different instances, indicating that a binding-competent state of the system is occasionally sampled. Simulations of the resulting singly-liganded systems reveal for the first time that the binding of one L-arg results in a holoprotein-like conformational distribution.

Permanent Link: http://hdl.handle.net/11104/0239206