title: Umbrella sampling simulations of biotin carboxylase: is a structure with an open ATP grasp domain stable in solution?
abstract: Biotin carboxylase is a homodimer that utilizes ATP to carboxylate biotin. Studies of the enzyme using X-ray crystallography revealed a prominent conformational change upon binding ATP. To determine the importance of this closing motion, the potential of mean force with the closure angle as a reaction coordinate was calculated using molecular dynamics simulations and umbrella sampling for a monomer of Escherichia coli biotin carboxylase in water with restraints to simulate attachment to a surface. The result suggests that the most stable state for the enzyme is a closed state different from both the ATP-bound and open state X-ray crystallography structures. There is also a significant motion of a region near the dimer interface not predicted by considering only open and closed configurations, which may have implications for the dynamics and activity of the dimer.
authors: Departments of Mechanical Engineering and Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA. bnovak1@lsu.edu
authors: Brian R
authors: BR
authors: Novak
authors: Dorel
authors: D
authors: Moldovan
authors: Grover L
authors: GL
authors: Waldrop
authors: Marcio S
authors: MS
authors: de Queiroz
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D019731:Carbon-Nitrogen Ligases / Q000737:chemistry* / Q000378:metabolism*; D004795:Enzyme Stability; D004926:Escherichia coli / Q000201:enzymology; D008958:Models, Molecular; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012996:Solutions
chemical_list: D012996:Solutions; D000255:Adenosine Triphosphate; D019731:Carbon-Nitrogen Ligases; C019791:biotin carboxylase