Theoretical Study on the ATP Hydrolysis Mechanism of HisP Protein, the ATP-Binding Subunit of ABC Transporter

Abstract

ATP binding subunit is known as a subunit of ABC transporter, providing energy through the binding of ATP with the subunit and the subsequent hydrolysis reaction of the bound ATP. In this study, density functional theory (DFT) method was used to study the ATP hydrolysis reaction in HisP protein, an ATP binding subunit of Histidine permease HisQMP 2 , by considering the ATP binding site, especially thephosphate group, surrounding residues and water molecules. Based on DFT calculations, we proposed that ATP hydrolysis is initiated by the formation of Mg 2þ mediated coordinate complex followed by the nucleophilic attack of a single water molecule (Water437) on the -phosphate; the hydrolysis product ADP acts as a leaving group. The transition state structure was determined by an approximate saddle-point search.

Nucleotide Activation of the Ca-ATPase

“…SERCA utilizes bimolecular nucleophilic substitution (S n 2) for phosphoryl transfer (67,83,84), a reaction mechanism that relies heavily on both the collisional frequency of the two reacting molecules and their orientation (83,85). SERCA hydrolyzes ATP at an extremely slow rate in the absence of Ca 2ϩ , suggesting that SERCA employs a mechanism to prevent nonproductive phosphoryl transfer in the Ca 2ϩ -free ATPase (6,45,86).…”