Umbrella Sampling Simulations of Biotin Carboxylase: Is a Structure with an Open ATP Grasp Domain Stable in Solution?

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• 作者：Brian R. Novak ; Dorel Moldovan ; Grover L. Waldrop ; Marcio S. de Queiroz
• 刊名：Journal of Physical Chemistry B
• 出版年：2009
• 出版时间：July 30, 2009
• 年：2009
• 卷：113
• 期：30
• 页码：10097-10103
• 全文大小：296K
• 年卷期：v.113,no.30(July 30, 2009)
• ISSN：1520-5207

文摘

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.