ISSN:
0020-7608
Keywords:
Computational Chemistry and Molecular Modeling
;
Atomic, Molecular and Optical Physics
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Some aspects of the catalytic mechanism of the serine proteases were submitted to ab initio RHF MO studies at a 3-21G basis set level. Analytical gradients were used to optimize the geometry of the molecular partners and to sense the interactions among them when they make up for the active site in chymotrypsin. Reaction fields of graded strengths were used to sense the response of the active site to protein surrounding effects. The catalytic triad (Asp-His-Ser) is reduced to a model dyad represented by ammonia and methyl alcohol. Methyl acetate represents a substrate. One water molecule is added to the model as a local solvation effect. (This molecule plays a central role in the rupture of the acylated enzyme, which was not studied here). The reaction pathways of MeAc interacting with the alcohol and alcoholate were studied to determine the intrinsic properties of this system in the present level of wave function representation. The presence of the dyad alters the interaction potential of the reacting system. The canonical form in vacuo is significantly more stable than the diionic one. The reaction field produces stabilizing effects favoring the catalytic diionic form. The effect of the tetrahedralization in the substrate has been studied. A planar substrate is strongly repelled at distances shorter than 3.0 Å, whereas a tetrahedral substrate can approach the catalytic dyad in the native configuration without apparent steric hindrance.
Additional Material:
6 Tab.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/qua.560330304
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