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Figure 4.
Fig. 4. The boot-shaped active-site cavity and putative
ammonium channel gate of the active conformation of plasmodial
ADA. (a) Side view of the cavity, looking into the side opposite
the catalytic zinc. The enclosed adenosine and DCF (yellow and
orange sticks, respectively) and water molecules (red spheres)
that occupy the cavity are displayed. The catalytic zinc
(magenta spheres) makes up one wall of the “heel” of the
boot. (b) The view has been rotated − 100° along the
y-axis and is now into the “toe” of the boot. Note that the
hydroxyl group of DCF that is equivalent to the leaving amine
group of adenosine is oriented toward the putative ammonium
channel. (c) The ammonia channel gate. Conformational changes in
α13 and in the side chain of Asp205 exist between the closed,
substrate-bound (d) and open, apo (e) forms of ADA. In the
closed form, the solvent-filled channel leading to the surface
from the active site is blocked by the side chain of Asp205.
When the enzyme is not bound to ligand, the Asp205 side chain
adopts an alternate conformation that allows the channel access
to the surrounding solvent, presumably facilitating the release
of the ammonia product.
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