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Proposition for the acylation mechanism of serine proteases: A one‐step process?
Author(s) -
Dive G.,
Dehareng D.,
Peeters D.
Publication year - 1996
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/(sici)1097-461x(1996)58:1<85::aid-qua9>3.0.co;2-u
Subject(s) - chemistry , ab initio , oxyanion hole , acylation , computational chemistry , serine protease , basis set , molecule , serine , stereochemistry , catalysis , protease , density functional theory , organic chemistry , hydrogen bond , enzyme
This work proposes a very detailed ab initio study of the hypothesis for a one‐step serine protease acylation process with one water molecule acting as the main catalyst reactant. For the 11 increasing complexity models considered, the minimum and transition state conformations for the reaction are determined by full geometry optimizations at the ab initio self‐consistent field ( SCF ) levels within several basis sets, from MINI‐1 to 6‐31G, and, for the smallest complexes, at the post‐SCF MP2 level within the 6‐31G** basis set. The related thermodynamical quantities are calculated for all the conformations. The influence of the oxyanion hole stabilizer and of the dyad His57‐Asp102 is quantified and a very good agreement is obtained with point mutagenesis. The activation barrier is found in the range 15–18 kcal/mol. © 1996 John Wiley & Sons, Inc.