A molecular orbital study on the complex between aspartic acid and histidine in the charge relay structure.

Abstract

α-Chymotrypsin, trypsin, elastase and acyl-α-chymotrypsin contain a charge relay structure composed of aspartate, histidine and serine or water ; in trypsin and elastase, histidine forms a bifurcated hydrogen bond with aspartic acid, while on the other hand, histidine of α-chymotrypsin forms a linear hydrogen bond. First, in order to determine the origin of the charge relay structure, the interaction energy between histidine and aspartate was calculated by the ab initio method. Since the bifurcated structure was much less stable than the linear one, it was suggested that reactions of enzymes containing the bifurcated hydrogen bond structure will occur via a linear hydrogen bond. The main contributors to the stability difference were the differences of electrostatic interaction energy and charge transfer energy. Moreover, the position of the proton between histidine and aspartate was determined by geometry optimization. Since the proton took a position midway between N of histidine and O of aspartate, the complex was named "hispartic acid." The interaction energy between water and hispartic acid was more stable than that between water and the histidine anion ; this was due to the differences of electrostatic interaction energy and exchange repulsion energy. Secondly, the interaction energies between water and histidine were calculated in detail ; the linear hydrogen bond structure was more stable than the bifurcated one. These energies were also decomposed in order to elucidate their origins.