The free Cn3D program can be used to identify putative active site residues. Examples are shown in the thumbnail images below of the tumor suppressor P53 complexed with DNA (accession 1TUP) and the prostaglandin H2 synthase protein bound to salicylic acid (accession 1PTH), showing the structural basis of aspirin activity. Click on either image to open a separate page with step-by-step instructions on how to generate that view, and see the Cn3D tutorial for additional details on how to use the program. In short:

1. Highlight a (bound) molecule of interest while viewing a structure in Cn3D. This can be done in several ways. For example, in the tumor suppressor image below, the DNA double helix was highlighted by using "mouse mode: select rows" in Cn3D’s "sequence/alignment viewer" window to select both of its nucleotide sequences. As a result, the double helix was highlighted in yellow in both the "sequence/alignment viewer" and structure view windows. In the prostaglandin H2 synthase image below, the salicylic acid molecule was highlighted in yellow by double clicking on it in the structure view window.



2. Use the "Show/Hide:Select by Distance" option to highlight amino acids within a specified distance (e.g., 5 Angstroms) of a molecule of interest. Those amino acids will then appear yellow in both the structure view and "sequence/alignment viewer" windows of Cn3D.

Note that the NCBI-curated data set in the Conserved Domain Database (CDD) also identifies amino acids involved in catalysis and binding whenever possible and describes their function in the conserved feature summary box of a conserved domain record. The specific amino acids involved in the conserved feature are marked with hash signs (#) in the domain model's multiple sequence alignment and highlighted in specially annotated 3D structures, when available.