Theoretical Insights on the Mechanism of the GTP Hydrolysis Catalyzed by the Elongation Factor Tu (EF-Tu)

The purpose of this work is to have a better understanding of the mechanism of GTP hydrolysis catalyzed by the elongation factor Tu. Two main aspects are being discussed in the literature: the associative or dissociative character of the process and the nature of nucleophile activation. The calculations of the QM subsystem have been done by means of the M06-2X density functional and the split valence triple-ζ 6-311+G­(d,p) basis set. The environmental effect has been introduced through the continuum SMD method. We have studied three models of increasing complexity in order to analyze the different factors that intervene in the catalytic action. The results obtained in this paper confirm that the protonated His84 plays a fundamental role in the catalytic mechanism, but we have also found that the crystallographic sodium ion has a notable effect in the catalysis. So, our work has permitted a new insight, complementary to those obtained with QM/MM calculations, into this very complex process.