Overview:
For this assignment, you must choose a paper from the scientific literature that describes the structure of a protein solved using X-ray crystallography. You will then write a report describing in your own words the structure of this protein and explaining what it tells you about the mechanisms of function. To support your report, you will create diagrams of the protein structure using the software, Pymol. These diagrams must effectively illustrate the structural/mechanistic features discussed in the paper. The third part of the assignment is to analyze the validity/accuracy of a protein structure.
For your assignment, Search in the literature for a paper that describes a recently solved protein structure using X-ray crystallography.
For example, a paper describing a recent structure of a serine protease is NOT acceptable. Also, consult the literature to learn about the mechanisms of function.
1) Write a short description of the overall fold of the protein and then discuss in greater detail the mechanism of function (It is therefore best if you choose a protein with a clear function). Maximum of one page single spaced, 12 point Times font, minimum margins of 1 inch (top, bottom, and sides).
2) Prepare diagrams using Pymol to illustrate the structure-function relationships discussed in (1). There is no restriction on the number of diagrams that you include, but you must be concise – so excess diagrams could lower your mark. You should illustrate the global fold of the protein and then illustrate key residues that are essential for function. Note that a substantial portion of your mark will be based on the effectiveness of the diagrams. So, zoom in on the important regions and make sure the diagrams effectively show in 3D details of what you are discussing in the text. Ensure your diagrams are well labelled. It is also a good idea to provide the reader with a sense of perspective. For example, if you show the global fold in Fig. 1 and zoom into a particular region in Fig. 2, then make sure the orientation of the protein in Figs. 1 and 2 are the same. You may want to circle the region in Fig. 1 that is shown in more detail in Fig. 2 so that the reader can easily see what you are trying to show.
Most students lose marks because their diagrams are not effective at illustrating key points. For an example of how to effectively present research findings, with excellent diagrams, please see the following article:
Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R., “The structure of the potassium channel: molecular basis of K+ conduction and selectivity” Science. (1998) 280:69-77. This structure along with additional work led to the awarding of the Nobel Prize in Chemistry to Roderick MacKinnon in 2003.
For example, how was the phase problem solved, etc.? Assess the accuracy of the structure using the parameters, such as resolution, R-factor, R-free, etc., discussed in class. Name the Bravais lattice and draw a picture of the unit cell labelling the dimensions and showing the possible location of atoms. Present the B-factor and Ramachandran plots. What do the plots tell you about the accuracy of the two structures? Look at the trends in the B-factor plot. Discuss how they correlate with the structure of the protein. (For comparison, look at the photoactive yellow protein structure solved at 0.85Å resolution by U.K. Genick et al. in 1998 (published in Nature)). Text can be up to 1 page single spaced, Diagrams extra.
https://www.rcsb.org/pdb/explore/explore.do?structureId=3q9l