Biotin carboxylase (BC) is part of acetyl-CoA carboxylase that catalyzes the first committed step in fatty acid biosynthesis. Although BC has been extensively studied, its mechanism is poorly understood. Because of its role in this crucial step a better understanding of its mechanism could be exploited to treat diseases such as obesity. The first step is the reaction of bicarbonate with ATP to produce a carboxyphosphate intermediate. When this reaction was modeled in vacuum, it was found to have a unrealistic energy barrier of 77.1 kcal/mol.  Lys238, Arg292, Glu296, and Arg338 residues have been implicated in the literature as being crucial to this mechanism and possibly involved in reducing this energy barrier. To test the ability of these residues to overcome this energy barrier, docking methods were used to find the placement of bicarbonate relative to the residues to develop quantum mechanical models for investigating lowering the energy barrier.

Docking of bicarbonate in the active site of biotin carboxylase

243rd National Meeting (2012)

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