Introduction - This script shows some aspects of the mechanism of
triose phosphate isomerase. Scroll down until the text corresponding
to the view is visible. (Based on 1ypi, E.Lolis et al. Biochem.
29 6609 (1990) & 2ypi, E.Lolis and G.A.Petsko Biochem.
29 6619 (1990).
Triose phosphate isomerase has an alpha/beta barrel structure with
an inner barrel of beta sheets and an outer barrel of alpha helices.
The active site residues are Lys 12, His 95 and Glu 165, which are
located on the outside of the protein.
In this view we see the enzyme in the absence (BLUE)
and presence (GREEN)
of a substrate analog (RED).
Note that only one loop (thick lines) moves when substrate binds.
Here is another view showing the interaction between the active site
residues and the substrate. Note how the loop (GREEN)
holds the substrate in place.
A closer look at the active site:
In this view we see the flexible loop over the substrate. The loop
holds the substrate in place and protects the enediol intermediate
from reacting with water.
Notice how the short helix (in BLUE)
is positioned relative to the substrate. The helix is essentially a
dipole and, as such, its positive end stabilizes the phosphate.
The short YELLOW
helix points toward His 95. The dipole
of the helix is such that its positive end orients toward the His,
effectively lowering its pKa.