UDP-Glc Dehydrogenase Studied in humans
1) Choose your topic: You are not limited to the choices above. However, the enzyme you choose must have the structure solved in an unliganded state and with at least one allosteric regulator molecule. More interesting projects are those for which there are man-made inhibitors as well.
2) Research the enzyme you have chosen
a) Search for information on your compound:
i. in Garrett and Grisham determine what pathway the enzyme is used in.
ii. find structure articles from the PDB
iii. Search on PUBMED for articles about the kinetics of the enzyme (see suppl. handout)
3) Everyone will present their enzyme both its kinetic regulation and its structural changes to the class as a PowerPoint presentation on the discussion board.
a) Your presentation should cover the following information:
(1) What pathway(s) is the enzyme used in?
(2) Is the ligand a natural regulator of the enzyme?
(a) Why does this compound regulate the enzyme?
(b) How is the regulation connected to the function of the enzyme and pathway?
(3) How does the binding of the ligand affect the structure (generate these structures yourself using PyMOL; you may use supplemental figures from papers, but you must have at least one image generated by you for the following three points):
(a) Show the structure un-liganded
(b) Show the structure with the ligand
(c) Highlight the changes and show slides that explain how the structure changes
(4) How is does the kinetics change when the ligand binds the enzyme?
(5) Is there evidence for either conformational selection or induced fit from this system?
(6) Have inhibitors been developed for this enzyme?
(a) What type of inhibitor(s)?
(b) Do the inhibitors change the conformation similar to the natural ligand?
(c) How does the inhibitor change the kinetics?
(7) Have mutation been made that change the binding of the ligand?
(a) What do these mutation analyses explain about the regulation of the active site of the enzyme?
(b) Are there mutations that alter the enzyme into a purely active or inactive state?
(8) What are the effects of changing this biochemistry within the target organism?
b) This material should be organized and structured using visual presentation. Organization should be obvious with sections for each of the topics: introduction, structural, kinetics and a conclusion.
c) At least half of your presentation should cover solid biochemistry material (see rubric). Sixty of the 100 points for the presentation are based on how well you explain the biochemistry.
d) The presentation should be 20–30 slides. Also include notes for the slides this can be in the form of a Word document, verbal files, or using the notes pages of PowerPoint. All information on the slides and in the notes should be referenced using a numerical style. So if the information in bullet point one came from Lipscomb et al. (2005) then site that at the end as #1 and put a #1 at the end of the bullet point. Images should be references like I do on my PowerPoint slides.
Warning: If you try using HL materials in an unethical manner, expect to fail your class. All HL items are old, recycled homework and are therefore not original. We intend them to be used only for the purposes of studying and learning.