Binding-competent states for L-arginine in E. coli arginine repressor apoprotein
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.
- MeSH
- Apoproteins chemistry metabolism MeSH
- Arginine chemistry metabolism MeSH
- Protein Conformation MeSH
- Ligands MeSH
- Escherichia coli Proteins chemistry metabolism MeSH
- Repressor Proteins chemistry metabolism MeSH
- Molecular Dynamics Simulation MeSH
- Molecular Docking Simulation MeSH
- Protein Binding MeSH
- Binding Sites MeSH
- Hydrogen Bonding MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Names of Substances
- Apoproteins MeSH
- Arginine MeSH
- ArgR protein, E coli MeSH Browser
- Ligands MeSH
- Escherichia coli Proteins MeSH
- Repressor Proteins MeSH
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.
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