A polypeptide in its cellular environment will spontaneously fold itself into a characteristic three-dimensional structure that is related to the purpose that it serves in the cell. In addition to the formation of secondary structures such as alpha helices and beta sheets, the secondary structures themselves move into particular positions within the folded polypeptide. The overall shape of the molecule is called tertiary structure. The positioning of parts of the polypeptide is influenced by interactions of hydrophilic R groups with water, attraction of hydrophobic R groups of one part of the polypeptide with another, and stabilization of the overall structure by disulfide bonds.
In the case of enzymes (catalytic proteins), the tertiary structure of the molecule produces an active site, a pocket which holds the substrate in a position favorable for facilitating the completion of the catalyzed reaction.
Many features of protein tertiary structure can be seen in the physical model of trypsin at the front of the classroom.
If you are viewing this on a portable device, you can take these notes and videos with you as you view the model:
Locate the amino and carboxyl terminal ends of the molecule. Trace the backbone for some distance to confirm that the entire molecule is one continuous chain.
Examine the location of R groups on the surface and the interior of the molecule.
Locate an alpha helix and part of a beta sheet.
Examine the active site. (Note: the video erroneously says that the substrate has a negatively charged end - it's actually positive.)
Possible effects of mutations.
Click on the link below to go to the search facility of the Protein Data Bank (PDB) Database at "Molecules To Go", an NIH database. When you click on the link, the modeling applet will open in a new window. You can resize that window and these instructions on the screen so that you can view both of them at the same time.
http://helixweb.nih.gov/cgi-bin/pdb
Enter "trypsin" as a search term, then press Enter. Click on the link labeled:
1AND ANIONIC TRYPSIN MUTANT WITH ARG 96 REPLACED BY HI
in the search results. This structure may be fairly far down the list, and you can use the browser's ""Find" function in the Edit menu to speed up finding the name. In the "Output requested" drop-down list, select JMOL PDB viewer. Then click on the "submit request" button.
Click on the following link to view a computer simulation of human tissue Kallikrien 4, a trypsin-like enzyme.
http://biology.kenyon.edu/BMB/Jmol2008/Paige_Anna/index.html
In the Contents section, click on III. Active Site.
