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 (GREEN) 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 (BLUE) holds the substrate in place.

 Note how Lys 12 binds the phosphate of the substrate.

 Note how Glu 165 is poised to abstract a proton from either C 1 or C 2 of the substrate.

 Note how His 95 is poised to accept a proton from either C 1 or C 2.

 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.

 Here we see how tightly this loop interacts with the substrate.

Notice how the short BLUE helix points toward the phosphate group of the substrate. The dipole of the helix is such that its positive end interacts with the phosphate. The short ORANGE helix points toward His 95. The dipole of the helix is such that its positive end points toward the His which lowers the pKa of the His.