抄録
The function of the hydrogen bond between His 57 and Asp 102 in serine proteases was studied by ab initio molecular orbital calculations on a model of the enzyme. The calculated hydrogen bond distance was 2.73Å, which is in good agreement with the distances obtained by X-ray diffraction analyses of trypsin. The stabilization energy is -30.0 kcal/mol. The electrostatic interaction term is the dominant contributor. The polarization energy and the charge transfer energy are also significant. The charge transfer energy is largely due to charge transfer from the aspartic acid to the histidine. The lone pair molecular orbital (LPMO) level of the nitrogen of His 57 increases substantially due to the electrostatic interaction between the two molecules. As a result, the charge transfer interaction between Ser 195 and the LPMO increases, and the increase of LPMO level should play a role in lowering the barrier height of proton transfer from Ser 195 to His 57 in trypsin. The populations of the LPMO upon complex formation are changed due to the polarization term. The populations of the outer shell of the nitrogen LPMO increase substantially, and hence the stabilization energy between His 57 and Ser 195 will increase with complex formation between His 57 and Asp 102. On the basis of optimized calculations of the complex, it is suggested that the hydrogen-bond structure in trypsin involves the anion of Asp 102, the neutral form of His 57 and the neutral form of Ser 195.
