QUANTUM-CHEMICAL STUDY OF THE CATALYTIC TRIAD IN SUBTILISIN - THE INFLUENCE OF AMINO-ACID SUBSTITUTIONS ON ENZYMATIC-ACTIVITY

In the catalytic reaction of serine proteases the basicity of a histid ine and the nucleophilicity of a serine, both residues together with a n aspartate residue belonging to the catalytic triad, are of great imp ortance. The influence of amino acid substitution on the basicity and the nucleophilicity of these important amino acids was investigated us ing a very simple and fast procedure. The amino acids of the triad wer e calculated at an ab initio level with the environmental residues rep resented by point charges obtained with the CHelpG population analysis . Basicity trends were found to be reflected by the charge on the basi c nitrogen and the ''protonation energy'', calculated for the triad. T he serine nucleophilicity was found to correlate with the charge on th e hydroxyl oxygen atom and with the minimum of the Molecular Electrost atic Potential in the vicinity of this oxygen. (C) 1998 Academic Press .