Friday, March 30, 2012

final post

Fructose1,6-bisphosphatase is a simple but elegant protein. Fructose1,6-bisphosphatase has been studied for a while because it is essential part of gluconeogenesis, which is the formation of glucose from smaller molecules. Fructose1,6-bisphosphatase converts fructose 1,6-bisphosphate to fructose 6-phosphate, by removal of a phosphate.This allows it to continue to the next steps until it is converted into glucose. This reaction might seem small and unimportant, however this enzyme is critical for controlling glucose levels in the body. Without it and gluconeogenesis, blood sugar would be harder to control.
One of the important structural features of fructose 1,6-bisphosphatase has multiple subunits that allows it to change from R state to T state.  The dimers shift 17 degrees from each other. This change the Arg-22 residue to go from interacting with Glu-108 and Arg-110 to Thr-27 and Glu-29. To see if the arginine was important part of the protein functionality, researchers at Boston College converted it to an alanine. They looked at the differences in the catalytic ability of R-state vs. T state. Through their research they found that the Arg22 to Ala has no effect on the enzyme and the R-state of the enzyme enhances catalytic potential. This research shows that the arginine is only part of the catalytic properties of the enzyme.

Figure1. (a)TheFBPaseisahomotetramer.Thethreepotentialtargets are shown: (1) the active site of FBPase, (2) the allosteric binding site of AMP, (3) the tetrameric allosteric inhibitor site. PDB coordinates 1KZ813,14 were used. The figure was drawn using POVScript+.37 (b) A closeup of the AMP binding pocket is shown. The three programs used are Dock6, Autodock4, and Surflex and were tested using the crystallographic ligand AMP moved out of the binding pocket (as explained in results section). This figure was drawn using POV- Script+.37 The three conformers of AMP were superimposed with a rmsd of <2.0 Å5 from actual AMP atoms in the crystallographic structure.

With an increase of obesity, fructose1,6-bisphosphatase may be a target for controlling diabetes. There are three targets that researchers at the University of Massachusetts are looking at, as seen in the figure, the active site, the allosteric binding site of AMP, and the tetrameric allosteric binding site. They have found that there are three heterocyclic organofluorine lead compounds. 
Fructose1,6-bisphosphatase may seem simple and not very significant, however it is a fascinating enzyme that plays an important part in the regulation of our blood sugar. Without it our bodies would have a difficult time keeping enough sugar in our blood.

Joseph Mendicino,* Fredrich Leibach, and Sesha Reddy, 1978 "Role of Enzyme Interactions in the Regulation of Gluconeogenesis: Phosphorylation of Fructose 1,6-Bisphosphataseand Phosphofructokinase by Kidney Protein Kinase?"

Aleksandra Rudnitskaya, Ken Huynh, Be ́la To ̈ro ̈k,* and Kimberly Stieglitz*
Novel Heteroaromatic Organofluorine Inhibitors of Fructose-1,6-bisphosphatase

Guqiang Lu, Mark K. Williams, Eugene L. Giroux, and Evan R. Kantrowitz"
Fructose-1,6-bisphosphatase: Arginine-22 Is Involved in Stabilization of the Allosteric State?


  1. This is just a comment on the layout of this entry. The last two photos are appearing as questions marks. I had this problem with my second entry and found that if I took screen shot directly to the blog it didn't work well. In order to correct this I took a screen shot pasted it in word saved the photo as a png and then imported it to the blog. Hope this helps.

  2. If you could provide figures of the mechanism that would be good, I know we covered in it class but a refresher would always be good. And you may have those already because it appears that you have two more images but all I am seeing is two white boxes.

  3. OK, same thing as the boys on the picture issue. I'm sure you can fix that. :) I really like the literature post, the old-school paper I thought was worth more explaing; what techniques did they use? What specifically from that research spurred on future research? The picutres are beautiful - it looks like a butterfly! Nice job! You make your protein proud!