Reaction Mechanism of the Guanosine Triphosphate Hydrolysis by the Vision-Related Protein Complex Arl3-RP2статья
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Дата последнего поиска статьи во внешних источниках: 9 июня 2016 г.
Аннотация:Complexes of the small GTPases with the GTPase activating proteins are intensively studied with the main focus on the complex of H-Ras with p120GAP (Ras-GAP). The detailed mechanism of the GTP hydrolysis is still uncovered. To clarify it we calculated the energy profile of the GTP hydrolysis in the active site of recently characterized vision-related member of this family, the Arl3-RP2 complex. The mechanism suggested in this study retains the main features of the GTP hydrolysis by the Ras-GAP complex, but the relative energies of the corresponding intermediates are different and additional intermediate exists in the Arl3-RP2 complex compared with the Ras-GAP. These differences arise from the small deviations of the catalytic arginine conformation in the active site. In the Arl3-RP2 complex two first intermediates, corresponding to the Pγ-Oβγ bond cleavage and the glutamine assisted proton transfer, are almost isoenergetic with the ES complex. Numerical simulations of the kinetic curves demonstrate that the concentrations of these intermediates are comparable with that of ES during the reaction. The calculated IR spectra reveal specific vibrational bands, corresponding to these intermediates. These specific features of the Arl3-RP2 complex open the opportunity to identify spectroscopically two more reaction intermediates in the GTP hydrolysis in addition to the ES and EP complexes.