User:Karsten Theis/detailed views

When analyzing the structure a biological macromolecule, there will be areas of special interest such as an active site of an enzyme, an unusual structural feature (cis-peptide, modified amino acids, covalent modifications), and binding sites for molecules small or large. This article shows some examples of how we can show these areas of special interest in detail, and will introduce the different visual elements used in these figures.

Detail of a bound ligand

One powerful way of learning about function from structural data is when the structure contains a bound ligand. Here, we first show the structure of the molybdenum cofactor of xanthine dehydrogenase. . Then, we show how it is bound to the enzyme . Color is a great way to add information to a figure. Here, we are coloring carbon atoms by subunit (large subunit in cyan and small subunit in violet), and all other atoms by element. This way, we use color to add two levels of information to the figure.

Adding interactions, distances, and labels

This is the same scene as before, but with even more information. Here is an example of the , an enzyme involved in nucleobase metabolism.

The scene is getting a bit crowded, so use the mouse to view from different angles, or click the wobble button a couple of times.

Some distances are crucial to function. Here is a picture of the and the approximate distances between them. Electrons travel from MoCo via to two-iron-two-sulfur centers to FAD as the substrate bound near MoCo is oxidized and FAD is reduced. If the distances between electron carriers were to large, or had to cross solvent-exposed areas, this enzyme would not work.

Surface view to show the shape of a binding pocket

One aspect of the binding specificity of proteins is shape complementarity of a binding site with the ligand. Here is an example of the , which can accommodate various nucleobases (some as substrate, some as inhibitors). The structure was solved in the presence of a suicide substrate that first gets oxidized on one side of the molecule, then rebinds to the molecule rotated by 180 degrees. The natural substrate gets oxidized on both sides, but the inhibitor (through a swap of a nitrogen and carbon atom) can not be oxidized at the second site.

Showing the rest of the molecule

In a static image, the rest of the molecule is often omitted, but in an interactive 3D figure, it is possible to show the detailed view in the context of the entire structure. The tricky part is to make sure that the overall structure does not interfere with the detailed view. There are several good ways to do this. One is to used very thin lines for the overall structure. Another is to show the overall structure in a transparent fashion. Finally, it is possible to turn on slabbing so that parts of the overall structure are visible in the plane of the detailed view, but not obscuring it in the front of it. Because the slabbing is dynamic, you will still see the details even if you rotate the view.

Superpositions

To show the differences between one active site and another (maybe of the same protein in a different crystal structure, or of a closely related protein), you can overlay (technical term: superimpose) the two structures and show both. Here is an from Garman lab: Interconversion of lysosomal enzyme specificities. Ball-and-stick is a great format because you can color the spheres showing the atoms (the ball in ball-and-stick) by element, and the bonds according to the color scheme used throughout a series of figures (e.g. by domain, by subunit, by which protein in case of this superposition). These superpositions get complicated, but you can easily animate them to switch back and forth between the two structures.

Electron density or other experimental information

See article on showing electron density in jmol. Here is another from Garman lab: Interconversion of lysosomal enzyme specificities.

Showing bonds, double bonds, metal binding sites, iron sulfur clusters

Sometimes you want to show bonds that are real but not automatically shown in the figure. Examples are covalent enzyme substrate complexes, iron-sulfur clusters or metal-metal interactions. Other times, you may want to show double bonds because they are important for a chemical reaction or for the properties of the structure. You will first have to add these bonds, and then you can show them.