Talk:HMG-CoA Reductase

From Proteopedia

Ideas for improvement

This "figure-review" was written by Jonathan Lafrenaye as part of an assignment for a Biochemistry course at Westfield State University, and posted here by the instructor with permission.

1. My favorite figure: My favorite figure was “E559 and D767.” The script for the figure can be located at wiki/scripts/HMG-CoA_Reductase/1dqa_e_and_d/2.spt. The figure is based off of the PDB code 1dq8. The primary citation for this figure is available at: Roitelman J, Olender EH, Bar-Nun S, Dunn WA Jr, Simoni RD. Immunological evidence for eight spans in the membrane domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase: implications for enzyme degradation in the endoplasmic reticulum. J Cell Biol. 1992 Jun;117(5):959-73. PMID:1374417
2. This is my suggestion for a figure legend: The active site of HMG-CoA reductase when bound to HMG-CoA. The Cis Loop is crucial in forming the active site with E559 and D767.
3. What I like about the figure: I liked this figure because it does a good job of showing the interactions with the cis loop in the active site of the reductase. The figure also does a good job of demonstrating how HMG-CoA binds in the active site. Understanding that statins are competitive inhibitors for this active site one gets a general idea of how statins bind to this reductase by viewing the HMG-CoA binding in this figure.
4. Corresponding figure in the primary citation: I could not find a corresponding figure for the development of this figure in the primary literature citation. However, I did my own research and found a figure that is a good representation of this figure with another angle and the binding with statins; this figure is figure 2 found at: Istvan, Eva S., and Johann Deisenhofer. “Structural Mechanism for Statin Inhibition of HMG-CoA Reductase.” Science, American Association for the Advancement of Science, 11 May 2001, science.sciencemag.org/content/292/5519/1160/tab-figures-data.
5. How I think the figure could be improved: This figure could be improved if it showed a few more residues in the active site. The corresponding paragraph that goes with this figure mentions important interactions with residue K691 in the active site. Additionally, tyrosine 479 is mentioned as having an important role of protecting the CoA from substrate solution. Both mentioned residues are not seen in this figure and would be beneficial additions to the figure in order to fully understand all of the interactions in the active site of the enzyme.

References

1. Istvan, Eva S., and Johann Deisenhofer. “Structural Mechanism for Statin Inhibition of HMG-CoA Reductase.” Science, American Association for the Advancement of Science, 11 May 2001, science.sciencemag.org/content/292/5519/1160/tab-figures-data.
2. Roitelman J, Olender EH, Bar-Nun S, Dunn WA Jr, Simoni RD. Immunological evidence for eight spans in the membrane domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase: implications for enzyme degradation in the endoplasmic reticulum. J Cell Biol. 1992 Jun;117(5):959-73. PMID:1374417

--Karsten Theis 20:35, 20 December 2018 (UTC)