Molecular orbital studies on serine, cysteine, and modified proteases.

Abstract

Molecular orbital studies were carried out on .alpha.-chymotrypsin, papain and thiolsubtilisin by using the complete neglect of differential overlap/2 method. By comparison between .alpha.-chymotrypsin and papain, the following results were obtained: the proton transfer barrier from Cys-25 (neutral) to His-57 (neutral) is lower than that from Ser-195 (neutral) to His-57 (anion) in the charge relay system of .alpha.-chymotrypsin; the active site of papain does not have the charge relay system and asparagine facilitates the proton transfer from cysteine to histidine. The results for thiolsubtilisin were as follows: the H-bond system structure in the active site is aspartate(neutral)-histidine(neutral)-cysteine(anion), and the charge relay system is broken by cysteine in place of serine; even though the effect of solvent is present, cysteine anion is stable. A charge relay system composed of aspartate, histidine and water dimer was proposed from the calculations by using water dimer in place of serine.