Ab initio study on the transition state of acylation step of trypsin catalysis.

The transition state of acylation step of trypsin catalysis was determined by molecular orbital calculations. The calculations were carried out at the RHF-LCAO-SCF approximation level with double zeta basis set (plus polarization functions). The role of His57 residue in the acylation step of the catalytic reaction of trypsin was analysed from a quantum mechanical point of view. The influences of surrounding residues, such as oxyanion hole and Asp102-, and the electrostatic effect of the other regions of the enzyme were also studied. His57 was proved to capture the proton from Ser195 side chain terminus with its lone pair and to transfer it to substrate with electrostatic assistance of Asp102- and oxyanion hole.