N5-CAIR synthetase is involved in the conversion of 5-amino-imidazole ribonucleotide (AIR), Mg2ATP and bicarbonate to N5-CAIR, Mg2ADP, and inorganic phosphate. In the first step of the reaction, carboxyphosphate is formed from nucleophilic attack of bicarbonate on the γ-phosphate of ATP. The original mechanistic proposals of electrostatic repulsion and hydrogen bonding at the transition state by Herschlag and Jencks are revisited. The reactions of γ-phosphorylated picoline with carbonate, acetate, and bicarbonate are modeled in the presence of magnesium ions and solvent in order to investigate the transition structure of this reaction. Computations were performed using both second-order Moller-Plesset theory and the M06-2X density function with Dunning’s jul-cc-pvnz (n = D, T, Q) basis sets. The studied mechanism involves an SN2 type transition state that has important implications within the enzymatic pocket of N5-CAIR synthetase. The results of this study are applied to study the reaction of bicarbonate and ATP within N5-CAIR synthetase.

Carboxyphosphate formation from the reaction of bicarbonate and ATP in ATP-dependent carboxylases

249th National Meeting (2015)

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