Link: http://www.rcsb.org/pdb/explore.do?structureId=1RZU

1. According to the Protein Data Bank, what class of enzyme is glycogen synthase? How can you explain (justify) this classification?

2. Check the sequence details. How many chains does glycogen synthase have, and what is its major class of secondary structure?

3. According to the abstract, what other enzyme does it resemble, and how does it differ from that enzyme?

4. If you do a search in the PDB for this other enzyme, you'll discover that it was once a molecule of the month. You can click on M and read about this other enzyme (recommended) or go to 1ygp to see an example of the structure. According to the abstract for 1ygp, an allosteric site can be occupied by either of two phosphoryl groups. What are the two groups, and why is their competition important?

This is due at the beginning of class on Monday, Dec. 1. Answers must be turned in individually.

Remember, please use these web sites as your sources of information and write short answers.

Answer:

1. Transferase (glycosyl transferase). A glucose residue is transferred from UDP to C4 in the nonreducing end of a chain in glycogen.

2. Two identical chains, 485 residues, 39% helical (20% beta sheet)

3. Glycogen phosphorylase; glycogen synthase has a wider cleft for the active site. Both are classified as transferases.

4. One is T (threonine)-phosphoryl, and the other is a phosphoryl group attached to glucose (glucose-6-phosphate). This is significant because when glucose-6-phosphate binds and displaces the phosphoryl group attached to T, the T-phosphoryl becomes a substrate for a phosphatase. When the phosphoryl group is removed, glycogen phosphorylase is more likely to be in the T (less active) conformation.

I have never seen a diagram that represents this, so this is the way I visualize it:

Additional comments: I couldn't fit all of the glucose-P into the allosteric site. Also I see that when I saved the file as a gif, it didn't save any of the P²⁻ that shold be showing inside the circle that is usually bonded to the glucose. If you look carefully, you should be able to find four places that should be labeled P²⁻. The vertical arrows are catalyzed reactions, while the horizontal arrows represent complex formation or dissociation.

Comments after grading:

1. A transferase isn't necessarily a kinase. Glycogen synthase transfers a glucose residue from UDP to the nonreducing end of a glycogen chain. This is a much more favorable reaction than adding glucose to the end of a glycogen chain.

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