PROTEINS Amino Acids

Amino Acid Molecular Structures
 Elmhurst College
Secondary Protein Structure Quaternary Protein Structure Denaturation  Chemistry Department
Tertiary Protein Structure Globular Proteins Minitopics  Virtual ChemBook

Tertiary Protein - Structure


The third type of structure found in proteins is called tertiary protein structure. The tertiary structure is the final specific geometric shape that a protein assumes. This final shape is determined by a variety of bonding interactions between the "side chains" on the amino acids. These bonding interactions may be stronger than the hydrogen bonds between amide groups holding the helical structure. As a result, bonding interactions between "side chains" may cause a number of folds, bends, and loops in the protein chain. Different fragments of the same chain may become bonded together.

There are four types of bonding interactions between "side chains" including: hydrogen bonding, salt bridges, disulfide bonds, and non-polar hydrophobic interactions.

Disulfide Bonds:

Disulfide bonds are formed by oxidation of the sulfhydryl groups on cysteine. Review reaction. Different protein chains or loops within a single chain are held together by the strong covalent disulfide bonds. Both of these examples are exhibited by the insulin in the graphic on the left.

Insulin Protein - Chime in new window

Hydrogen Bonding:

Hydrogen bonding between "side chains" occurs in a variety of circumstances. The most usual cases are between two alcohols, an alcohol and an acid, two acids, or an alcohol and an amine or amide. In giving the structures for various examples, the backbone of the protein fragment will be represented by a short helix with only the side chain structure given as in the graphic on the left.

In the prion protein, tyr 128 is hydrogen bonded to asp 178, which cause one part of the chain to be bonding with a part some distance away.

Prion Protein - Chime in new window

Examples of amino acid side chains that may hydrogen bond to each other:

Two alcohols: ser, thr, and tyr.
Alcohol and an acid: asp and tyr
Two acids: asp and glu
Alcohol and amine: ser and lys
Alcohol and amide: ser and asn

Quiz:Name other amino acids that may engage in hydrogen bonding. Other answers are possible
Alcohol and Acid?
Alcohol and Amine?  
 Alcohol and Amide?  

Salt Bridges:

Salt bridges result from the neutralization of an acid and amine on side chains. Review reaction. The final interaction is ionic between the positive ammonium group and the negative acid group. Any combination of the various acidic or amine amino acid side chains will have this effect.

The example on the left is from the prion protein with the salt bridge of glutamic acid 200 and lysine 204. In this case a very small loop is made because there are only three other amino acids between them. This salt bridge has the effect of straightening an alpha helix.

Prion Protein - Chime in new window


Quiz:Name other amino acids that may engage in salt bridges. Other answers are possible



Click for larger image 

 Non-Polar Hydrophobic Interactions:

The hydrophobic interactions of non-polar side chains are believed to contribute significantly to the stabilizing of the tertiary structures in proteins. This interaction is really just an application of the solubility rule that "likes dissolve likes". The non-polar groups mutually repel water and other polar groups and results in a net attraction of the non-polar groups for each other. Hydrocarbon alkyl groups on ala, val, leu, and ile interact in this way. In addition, benzene (aromatic) rings on phe and tyr can "stack" together.

In many cases this results in the non-polar side chains of amino acids being on the inside of a globular protein, while the outside of the proteins contains mainly polar groups.

Insulin Protein - Chime in new window

Prion Protein - Chime in new window

Quiz: Name other amino acids that may engage in hydrophobic interactions. Other answers are possible.