The Peptide Bond

Amino acids can be joined together to form a peptide or polypeptide. They are called peptides because when the carboxyl group of one amino acid joins to the amino group of another, a peptide bond is formed. Chemically this is an amide bond but when it occurs in proteins it is given the name peptide bond.

In a polypeptide, there are many peptide bonds. These bonds are rigid and planar, due to electron sharing between the carboxyl carbon and the amide nitrogens which contribute to the bond and give it a partial double-bond character.

For Example:-
(Note, the images will be displayed in the frame at left when the buttons below are pressed. The hydrogens are have been omitted from the structures for simplicity)

Lysine

Lysine with Phenylalanine

select all Dipeptide

Have a look at the plane of the peptide bond (that's the bond which appeared when you clicked the last button) by rotating the image slowly. (You will see the planar nature of the bond better if you use the Chime pop up menu to change the display to "Sticks"
Notice it is planar/flat. The reason for the planar nature of the peptide bond is that it is a partial double-bond. The electrons from the double bond to Oxygen migrate to the bond between the C and the N producing partial + and -ve charges on the N and O. This is shown in the diagram of the dipeptide below.

The partial double bond nature of the peptide bond means that there is not free rotation about the C -- N bond. The most stable conformation is planar and trans as shown in the diagram

Note that he dipeptide still has an a amino group at one end (on the lysine) and an a carboxyl group at the other end (on the phenylalanine. These are called the termini. Each peptide chain has one amino terminus and one carboxyl terminus. These are the only free a amino and a carboxyl groups in the peptide. All of the others are involved in the peptide bonds between amino acids. (Note that lysine has an amino group on its sidechain.)

This means that the peptide chain (a.k.a. polypeptide) has direction. The chains are written schematically from the amino terminus to the carboxyl terminus, as below.

N-Lys-Phe-Gln-Leu-Phe-C

When amino acids are in a polypeptide chain, they are referred to as "residues". And you can see in the above image, that there is no restriction on the types of residues which are linked.

The next image has the sidechains coloured to show the individual atoms and the backbone of the peptide is shown in yellow. As you can see, the backbone forms a regular repeating unit ( ) shown in the yellow colour.
(You can see this better is you change the colour to "CPK" using the pop up menu in the structure frame.)
The rest of the polypeptide consists of the sidechains.

There is no set length of a polypeptide (how long is a piece of string) although most polypeptides in nature are between 50 and 2000 residues long.

Primary Structure

A protein has a completely defined order of amino acids, called its sequence. For instance in the above polypeptide the sequence is: Lys-Phe-Gln-Leu-Phe.

This defined sequence is called the primary structure of the protein. This is often abbreviated as (1^o). The sequence, or primary structure is specified by the sequence of the piece of DNA containing a gene for that protein, and the sequence is unique to the individual protein.

All the information necessary to make a protein is contained in the primary structure. However as we shall see soon the primary structure is only the first level of structural complexity of proteins.

ALTERATIONS IN PRIMARY STRUCTURE

The primary structure of a protein (amino acid sequence) contains all the information needed to make the protein into a complicated 3 dimensional shape (similar to those you saw in the first tutorial). This shape is essential to the function of the protein.

Therefore it is conceivable that an alteration to the primary structure, could have an incredibly damaging effect on the protein, and consequently on the cell or the body in which the damaged protein is located.

If the cell no longer has a fully functional, correctly folded protein then some sort of physiological derangement of the normal functioning of the cell may occur..

For Example:
Haemoglobin is a carrier protein which you probably remember from the first part of the tutorial. If one amino acid is altered in the b -chain of the protein, from Glu --> Val, the haemoglobin protein becomes much less soluble. especially when it is not carrying oxygen. (the bright pink residue is the Glu on the normal form of the protein which is mutated to Val in the sickle cell form)

Individuals who carry this mutation on both genes for the bsubunit have a syndrome called sickle cell anaemia in which the insoluble haemoglobin precipitates in the red cells and the red cells assume a sickle shape. These miss-shapen red cells block capililaries and the red cells are destroyed, leading to the anaemia.

Sickle cell anaemia is a very debilitating syndrome and individuals both genes mutated in this way often die at a young age. However, in certain part of Africa there is a very high incidence of the gene for sickle cell anaemia. It has been shown that individuals who have only one mutant gene for the b-haemglobin often do not have the severe symptoms of sickle cell syndrome and the presence of the single mutant gene protects them, in a way which is not fully understood, from a particularly lethal form of malaria which is prevelant in the same regions in Africa.

Another Example:
Cystic Fibrosis is a respiratory disease for which there is no cure, and often results in death before the age of 20. This is caused by a change in primary structure of a membrane transport protein, which results in a defective membrane channel. In most cases the damage is done by the loss of a single amino acid from the protein sequence.

So you can see that the correct primary sequence of a protein is very important and any alterations to the sequence can have disastrous effects on the body. This is because structure is important for protein function, and any change in the amino acid sequence often affects the 3 dimensional (3D) structure of the protein.

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