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We have studied the binding of two inhibitor molecules, imidazole and
1,10-phenanthroline, to liver alcohol dehydrogenase by crystallographic methods.
X-ray data for the imidazole complex were collected to 0.29-nm resolution and
for the 1,10-phenanthroline complex to 0.45-nm resolution. In both cases we
found only one peak in the difference electron density maps close to the active
zinc atom. The peak corresponding to 1,10-phenanthroline overlaps the site of
the density of the zinc-bound water in the apoenzyme and the imidazole density
partly overlaps this density. We can not discern any additional peaks close to
the zinc atom which would correspond to new positions of bound water. We thus
conclude that both these inhibitors bind to the catalytic zinc atom and that
upon binding they displace the water molecule that is firmly bound to this zinc
atom in the apoenzyme. We do not see any structural changes in the remaining
part of the molecule.
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