Binding-competent states for L-arginine in E. coli arginine repressor apoprotein

Saurabh Kumar Pandey, David Řeha, Vasilina Zayats, Milan Melichercik, Jannette Carey, Rüdiger Ettrich

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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 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.

Original languageEnglish (US)
Article number2330
JournalJournal of Molecular Modeling
Issue number7
StatePublished - Jul 2014

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Computational Theory and Mathematics
  • Inorganic Chemistry


  • Allostery
  • ArgRC
  • Conformational dynamics
  • Principal components analysis
  • Salt bridges
  • Temporal evolution of conformers


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