物理化学学报 >> 1989, Vol. 5 >> Issue (04): 385-387.doi: 10.3866/PKU.WHXB19890401

通讯    下一篇

关于静电作用对酶活性部位残基pKa影响的定量计算

来鲁华; 罗宇; 徐筱杰; 邵美成; 唐有祺   

  1. 北京大学物理化学研究所
  • 收稿日期:1989-01-28 修回日期:1989-03-31 发布日期:1989-08-15
  • 通讯作者: 徐筱杰

THE QUANTITATIVE CALCULATION OF ELECTROSTATIC EFFECT ON THE pKa OF ACTIVE SITE RESIDUES IN ENZYMES

Lai Luhua; Luo Yu; Xu Xiaojie*; Shao Meicheg; Tang Youqi   

  1. Institue of Physical Chemistry; Peking University; Beijing 100871; China
  • Received:1989-01-28 Revised:1989-03-31 Published:1989-08-15
  • Contact: Xu Xiaojie

Abstract: Kirkwood theory was applied to investigate the influence of substituting surface charged groups in protein engineering on pK_a of active site residues in enzymes. An expression was obtained to calculate the change of pK_a quartitatively, which was successfully used in calculating the change of pK_a of histidine in the active site in subtilisin and trypsin. The results of subtilisin agrees with experimental data well When surface positive residues were changed to neutral or negative ones, the pK_a would be raised; and when surface negative residues were changed to neutral or positive ones, the pK_a would be lowered. There is an obvious relationship between the position of surface chares and the change of pK_a. For trypsin, when surface charges are within a cone with a base angle of 70°around His (57), the pK_a of His (57) will be changed remarkablly. Four mutants in rat-trypsin were selected as potential sites to raise the pK_a of His (57).