Structure Comparisons

With the crystal structure of both forms of the FBPA/P enzyme obtained they could be compared and contrasted.

When the FBP bound form (green) and the DHAP bound (cyan) form are superimposed they are seen to be very similar. However when we look more closely we can see the differences in the active site where the three loops are not perfectly aligned.

Similarities between the structures
Both crystals forms are very metamorphous meaning that they have very similar structure and their monomer structures are identical. The ternary and quaternary structures are also the same for both forms of the enzyme. 


Differences between the structures
For both structures magnesium ions are very important in ensuring catalytic function of FBPA/P. The first difference in the structures is displayed by how these magnesium ions are arranged. DHAP phosphate group coordinates the 3 magnesium ions in FBPA whereas in the FBPase form the FBP phosphate coordinates 4 magnesium ions: in the FBPA form of the enzyme a magnesium which is essential for the catalysis of FBPase is flipped out of the active site. As you will see later, this is important for the enzyme site metamorphosis.

The second significant difference is to do with the three loop regions which are located in the active site of both structures. The loop regions show a greater flexibility compared with the rest of the protein, shown by the B factors. They consist of; a lid loop, a Schiff base loop and a C-terminal loop. 

On the left the FBPase form of the enzyme is shown where the FBP would bind. The lid (blue) and C terminal (pink) loop are interacting with the substrate and stabilizing its binding while the Schiff loop (red) has been pushed out of the active site allowing Mg1 to bind. In contract on the right we can see the FBPA form of the enzyme where DHAP would bind. The Schiff loop (red) is cutting across the active site and forming a Schiff base with the substrate and the lid (blue) and C terminal (pink) loops are located away from the active site.