A site, or functional site, is region in a three-dimensional protein structure that performs a function. The site is composed of a cluster of amino acids, but non-amino-acid components may also be required for function (such as metal ions). Typical sites could be catalytic sites that bind substrates in enzymes, regulatory sites that bind regulatory factors, sites that bind non-protein entities such as metal ions, and sites that bind nucleic acids or other proteins. Functional sites are usually evolutionarily conserved, but are sometimes evolutionarily hypervariable.
Sites Green Links
The Sites green links in Proteopedia highlight the residues (as sticks) that make up functional sites as defined in the PDB file being displayed. You may have to zoom in to see them clearly. For example, at 1eve, below the molecule, are green links to highlight a catalytic site, and an inhibitor binding site. These two sites were abbreviated in the atomic coordinate file as CAT and IHB, respectively. Clicking on the green links displays the full name of the site immediately below the molecule.
Identifying Residues in Sites
You can identify the residues in the site by touching them on the 3D structure itself (not clicking them) with the mouse. A small box, called a "hover report", will appear in a few seconds, identifying the atom, residue, and chain touched with the mouse. Any atom can be identified in this way, regardless of whether it is in a site. In order to be sure you have touched the intended atom, you must be careful that the mouse is not near other atoms. This is best accomplished by positioning the molecule so that the atom of interest has nothing in front of it, and has only blank background behind it.
In order for Proteopedia to be able to highlight functional sites, the authors of the atomic coordinate file must have defined these sites when the file was published. Often, authors may not have defined known functional sites in the atomic coordinate file when they published it. Sometimes, the structure may have been determined before functional sites were known, and hence they will be absent in the atomic coordinate file. Thus, the absence of green links for Sites does not mean that there are no functional sites.
Of course, in Proteopedia, when a known functional site was not included in the atomic coordinate file, it is relatively easy to add a green link that shows it.
Detecting Functional Sites
One way to look for functional sites in a protein structure is to look for surface patches of highly conserved residues. This can be done automatically with the ConSurf Server. See Conservation, Evolutionary.
Exploring Binding Sites
Many of the sites with green links in Proteopedia are binding sites. If you wish to explore a binding site in more detail, try the link to FirstGlance in the Resources line beneath the interactive molecule (on all pages titled with a PDB code). Or simply go to FirstGlance.Jmol.Org and enter the PDB code.
Once in FirstGlance, click on Contacts. Follow the instructions there to display all the atoms and residues that are likely noncovalently bonded to any moiety you choose. An example showing the contacts to an enzyme-bound drug will be found at Help:Copying_FirstGlance_Scenes_into_Proteopedia.