posted on 2016-02-21, 18:22authored byMaria E. Rudbeck, Sten O. Nilsson Lill, Andreas Barth
A protein environment can affect the structure and charge
distribution
of substrate molecules. Here, the structure and partial charges were
studied for different phosphorylated amino acid models in varying
environments using density functional theory. The three systems investigated,
acetyl phosphate, methyl phosphate, and p-tolyl phosphate
are representative models for aspartyl phosphate, serine or threonine
phosphate, and tyrosine phosphate, respectively. Combined with the
CPCM continuum model, explicit HF and H2O molecules were
added in order to model environmental effects and interactions that
may occur in a protein matrix. We show how the different interactions
affect the scissile P–O(R) bond and that the elongation can
be explained by an anomeric effect. An increasing scissile bond length
will result in transfer of negative charge to the leaving group and
in a widening of the angle between the terminal oxygens of the phosphate
molecule, features that can expose the phosphate group to attacking
nucleophiles. Lastly, calculations were performed on the active site
of the Ca2+-ATPase E2P intermediate, which provide an example
of how a protein environment facilitates the formation of a destabilized
ground state.