Title

Umbrella sampling simulations of biotin carboxylase: is a structure with an open ATP grasp domain stable in solution?

Document Type

Article

Publication Date

7-30-2009

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.

Publication Source (Journal or Book title)

The journal of physical chemistry. B

First Page

10097

Last Page

103

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