Trios Phosphate Isomerase Structure and Function

Triose Phosphate Isomerase is an enzyme which is extremely useful in the glycolytic pathway. Glycolysis is a metabolic pathway where organisms extract energy in the form of ATP during the conversion of glucose into pyruvate and lactate. Glycolysis helps supply the body with energy that it needs.Trios Phosphate aids in catalysis by binding tightly to the enediol transition state. To convert GAP to the enediol intermediate, a proton is abstracted from C2 by a a Glyceraldehyde 3 phosphate base, the active site which is near carboxyl group, and the carbonyl oxygen atom is protonated by an acid.[4]

The process is better understood when followed step by step. First, glyceraldehyde-3-phosphate binds to the active site near the carboxyl group, then enediol intermediates (Glu 165) picks up the C2 photon and in the process HA donates a proton to make a carbonyl oxygen. Then a proton is returned and once it is accepted a DHAP is made.Its quaternary structure is a homodimer, which means it is a protein composed of two polypeptide chains. Trios Phosphate has a very interesting structure that is important to its function. Its secondary structure has 14 alpha helices and 8 beta sheets. Its tertiary structure is an alpha-beta barrel in which beta barrels are surrounded by alpha helices in between the beta strands. They are intertwined in a way and they create a barrel shape which is called “TIM Barrel”.

This is a picture of an active site which is Glu 165 and in this spot is where the enzyme grabs the C2 proton.

The photo above shows the “TIM Barrel” shape in which the alpha helices wrap around the beta sheets. In proteins with this “TIM Barrel” structure, the loops at the C-terminal ends of the parallel beta-strands form the active site.

The loop formed by residues 167 (circled) to 176 (labeled), close over the active site and it does not allow the phosphate to leave during the enediol intermediate. Without the loop, the phosphate could escape and the DHAP would not be made.