Hydration effects on proton transfer reactions in the catalytic triad Ser-His-Glu

Abstract

Abstract An in-depth understanding of irradiation effects on DNA and enzymes is important in elucidating the effect of radiation exposure on humans and animals. The catalytic triad Ser-His-Glu is composed of amino acids serine (Ser), histidine (His), and glutamic acid (Glu). In the present study, the radiation effects on Ser-His-Glu have been investigated theoretically using ab initio and direct ab initio molecular dynamics (AIMD) methods. In addition, the effects of micro-solvation in Ser-His-Glu were studied, because X-ray diffraction experiments revealed that one water molecule is located near Ser-His-Glu. Based on geometry optimizations, it was determined that the presence of the H2O molecule results in two structures: a structure wherein the H2O molecule is added to the Glu position of Ser-His-Glu (H2O(A)), and the one wherein the molecule is bonded to the Ser position (H2O(B)). The reaction dynamics after hole-capture were calculated for three structures including the unhydrated structure of Ser-His-Glu (no-H2O). For these structures, the proton transfer (PT) from His to Glu occurred after hole-capture. The PT rate of the no-H2O and the H2O(B) was within 10 fs, whereas that of the H2O(A) was 15 fs. This is indicative of the effect of micro-solvation on the PT time in Ser-His-Glu. The reaction mechanism was discussed based on the theoretical results.