Binding-competent states for L-arginine in E. coli arginine repressor apoprotein
Saurabh Kumar Pandey1,2, David Řeha1,2,
Vasilina Zayats1,2, Milan Melichercik1,3, Jannette Carey1,4*, Rüdiger
Ettrich1,2*
1Institute of Nanobiology and Structural Biology, Global Change Research Center, Academy of
Sciences of the Czech Republic, Zamek 136, CZ-373 33 Nove Hrady, Czech Republic
2Faculty of Sciences, University of South Bohemia in Ceske Budejovice, Zamek 136, CZ-373 33 Nove
Hrady, Czech Republic
3Department of Nuclear Physics and Biophysics, Comenius University, Mlynská dolina F1, 842 48
Bratislava, Slovak Republic
4Chemistry Department, Princeton University, Princeton, New Jersey 08544-1009, USA
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 ~50 kDa hexameric C-terminal domain was studied by 100 ns molecular dynamics simulations in 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.