Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains

A series of amino acids joined by peptide bonds form a polypeptide chain, each amino acid unit in a polypeptide is called residue.

A Polypeptide chain has a polarity because its end are different, with amino group at one end and carboxyl group at the other hand.

In some proteins, the linear polypeptide chain is cross-linked by ox-red reaction of cys A polypeptide chain consists of regular repeating part, called the main chain or backbone, and variable part, comprising the distinctive side chain. The polypeptide backbone is rich in hydrogen bonding potential. Each residue contains carbonyl group, which is a good hydrogen bond acceptor, and an NH group which is a good hydrogen bond donor.

Proteins Have Unique Amino Acid Sequences Specified by Genes

Frederic Sanger determined amino acid sequence of insulin in 1953. The striking fact is that each protein has a unique, precisely defined amino acid sequences. The amino acid sequence of a protein is often referred as its primary structure. Why is it important to know the amino acid sequences of a protein? 1. Knowledge of the sequence of a protein is usually essential to elucidating its mechanism of action 2. Amino acid sequences determine the 3-D structures of proteins. 3. Sequence determination is a component of molecular pathology.

Studies in the late of 1950 revealed that amino acid sequences of proteins are genetically determined. The sequence of nucleotide in DNA specifies a complementary sequences in RNA, which in turn specifies amino acid sequence of a protein.

Polypeptide Chains Are Flexible yet Conformationally Restricted

The peptide bond is essentially planar. Thus for a pair of amino acid linked by a peptide bond, six atoms lies in the same plane: alpha carbon atom and CO group from the first amino acid and the NH group and alpha carbon atom from the second amino acid The nature of the chemical bonding within a peptide explains this geometric preference. The peptide bond has considerable double bond character, which prevents rotation about this bond.

The inability of the bond to rotate constrains the conformation of the peptide backbone and accounts for bonds planarity. The double bond character is also expressed in the length of the bond between the CO and NH group. Finally, the peptide bond is uncharged, allowing polymers of amino acids linked by peptide bonds to form tightly packed globular structure.

Two conformation are possible for a planar peptide bond: trans and cis configurations

In contrast with the peptide bond, the bonds between the amino and the alpha carbon atom and between the alpha carbon atom and the carbonyl group are pure single bond.

Are all combinations of and ? Ramachandran recognized that many combinations are forbidden because of steric collisions between atoms.

phi ()=The angle of rotation about the bond between the nitrogen and alpha carbon atoms psi ()= The angle of rotation about the bond between carbonyl and alpha carbon atoms

Secondary Structure
There are two periodic structure found in proteins: alpha helix and beta plated sheet. Subsequently, other structures such as the beta turn and omega loop were identified.

The Alpha Helix Is a Coiled Structure Stabilized by Hydrogen Bond

Alpha helix is a rod like structure and stabilized by hydrogen bonds between the NH and CO groups of the main chain or backbone.

Each residue related to the next by a rise of 1.5 along the helix axis, which give 3.6 amino acid residues per turn of helix

The Ramachandran diagram reveals that both the right- and left-handed helices are among allowed conformation. However, right handed helices are energetically more favorable because there is less steric clash between the side chains and the backbone.

Essentially all alpha helices found in proteins are right-handed

The alpha helical content of proteins ranges widely, from nearly none to 100%. For example 75% of the residues in ferritin are in alpha helices.

Beta Sheets Are Stabilized by Hydrogen Bonding Between Polypeptide Strands

A -sheet is formed by linking two or more -strands by hydrogen bonds. In anti parallel arrangement, the NH group and the CO group of a partner on the adjacent chain.

-sheet is almost fully extended rather than being tightly coiled as in the alpha helix.. The distance between adjacent aa along a beta strand is approximately 3.5 , in contrast with a distance of 1.5 along a alpha helix. The side chains of adjacent aa point in opposite direction.

In the parallel arrangement, the hydrogen bonding scheme is slightly more complicated. For each amino acid, the NH group is hydrogen bonded to the CO group of one amino acid on the adjacent strand, whereas the CO group is hydrogen bonded to the NH group on the amino acid two residue apart.

Since beta strands are extended fully, a range of extended structures are sterically allowed.

Many strands, typically 4 or 5 but as many as 10 or more, can come together in beta sheet. Such beta sheet cab be purely antiparallel, purely parallel or mixed

Fatty Acid binding protein

Polypeptide Chains Can Change Direction by Making Reverse Turns and Loops
Most proteins have compact, globular shapes, requiring reversal in the direction of their polypeptide chains. Many of these reversals are accomplished by a common structural element called reverse turn. This interaction stabilize abrupt changes in direction of polypeptide changes.

More elaborate structures are responsible for these structures are called loops or sometime omega loops.