Chemistry Reference
In-Depth Information
Fig. 12 Structure of the reversible enzyme-inhibitor complex. As indicated, the thiolate may
attack at the C
a
and C
b
(C2 and C3) carbon atoms
The resulting structure of the reversible enzyme-inhibitor complex is given in
Fig.
12
. In this figure, we use the same representation as in Fig.
11
.
The structure of the computed reversible inhibitor-enzyme complex cannot be
directly compared with experimental data as X-ray experiments are not feasible.
However, the computed data for the inhibition reaction agreed with all relevant
experimental results about the regio [
131
] - and the stereochemistry [
132
] of the
inhibition process, the influence of the pH value of the environment [
133
], and
trends in the potencies of the inhibitors. The agreement for this multitude of
properties strongly supports the reliability of the computed structure. Further details
on the preparation procedure and the computations of the reaction paths are
described elsewhere [
134
].
In the next step, the QM/MM approach was applied to compute the EDs of the
inhibitor in the reversible enzyme-inhibitor complex. The calculations were per-
formed as for AMCHA. For a comparison of the situation within the enzyme with
the one in vacuum and solvent, E64c was also computed for these environments.
The geometrical arrangements are given elsewhere [
83
].
