Lectures 5

Peptides and Proteins (Part 1)

1. Introduction:
Proteins are organic molecules formed by the linking together of a large number of
amino acids to form long chains.
Proteins are present in every cell of humans, animals, plant tissues, tissue fluids and in
microorganisms.
They account for about 17% of body weight.

2. Functions of Proteins
a) Enzymes catalyze chemical reactions in the body. For example, the digestive enzymes
pepsin, trypsin, and chymotrypsin break down proteins in our diet

b) Antibodies (also called immunoglobulins), involved in defense function are produced

in response to foreign antigens (bacteria and viruses).

c) Transport proteins carry materials from one place to another in the body. For
example, the protein transferrin transports iron from the liver to the bone marrow.
Hemoglobin is responsible for transport and storage of oxygen.

d) Regulatory proteins control many aspects of cell function, including metabolism and
reproduction. Many of the hormones that regulate body function, such as insulin and
glucagon, are proteins.

e) Structural proteins provide mechanical support to large animals. Our hair and
fingernails are largely composed of the protein keratin.

f) Movement proteins are necessary for all forms of movement. Our muscles contract
and expand through the interaction of actin and myosin proteins.

g) Nutrient proteins serve as sources of amino acids for embryos or infants. Egg albumin
and casein in milk are examples of nutrient storage proteins.

h) Proteins act as buffers such as plasma proteins and thus help to regulate acid-base.

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3. Peptides
Peptides consist of 2 or more amino acid residues linked by peptide bond (amide bond).
Proteins are linear polymers of L-α-amino acids.
The carboxyl group of one amino acid reacts with the amino group of another amino
acid, undergoing a condensation reaction that forms a peptide linkage.

The peptide bond is planar and rigid because the pair of electrons of the nitrogen atom
interacts with the carbon and oxygen of the carbonyl group. This gives the peptide bond
a partially double bond character.
This is important physiologically because it makes protein structures relatively rigid:

When a polypeptide is named, all amino acid residues have their suffixes (-ine, -an, -ic,
or -ate) changed to –yl, with the exception of the C-terminal amino acid. For example, a
tripeptide composed of an N-terminal valine, a glycine, and a C-terminal leucine is
called valylglycylleucine and written simply as Val-Gly-Leu.
A polypeptide chain consists of a repeating part, called the main chain (backbone) and a
variable part, the side chain.
If the number of amino acids in a polypeptide is 50 or less, the molecule is known as a
peptide; if the sequence is more than 50 amino acid units, it is known as a protein.

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4. Classifications of Proteins
4.1 Classifications of proteins based on organization:
A) Primary structure:
Primary structure of the protein is the linear sequence of amino acids in the
polypeptide chain joined together by peptide bonds.

Understanding the primary structure of proteins is important because many genetic

diseases result in proteins with abnormal amino acid sequences, which cause loss of normal
function.
Bonds responsible for the maintenance of primary structure are mainly peptide
bonds and disulfide bonds. Both of them are covalent bonds.
Primary Structure of Insulin: This protein consists of two polypeptide chains A
and B held together by two disulfide links. The two chains are covalently linked by
disulfide bonds. The A chain has N-terminal glycine and C-terminal aspargine. The
B chain has phenylalanine and alanine as N-and C-terminal residues, respectively.

Figure 5.1. The hormone insulin consists of two polypeptide chains, A and B, held together by
two disulfide cross-bridges.

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 B) Secondary structure
The secondary structure of a protein is a three-dimensional shape that results from
hydrogen bonding between the amino and carboxyl groups of adjacent amino acids.
The α-helix, β-sheet, and β-bend are examples of secondary structures of proteins.
Most globular proteins contain segments of α-helix or β-pleated sheet separated by
kinks of random coil, allowing the molecule to fold into its globular shape.
(i) α-helix:
 The α-helix is a rigid, rod-like structure that forms when a polypeptide chain
forms hydrogen bonds.
 For example, the fibrous protein α-keratin is arranged in the α-helical structure,
and most globular proteins contain segments of α-helix (Figure 6.2).

Figure 5.2. Schematic diagram showing only the helical backbone.

(ii) β-pleated sheet

 In a β-pleated sheet, two polypeptide backbones are folded and aligned next to
each other forming hydrogen bonding between the two chains.
 β-pleated sheets are either parallel or antiparallel β-folding.

Figure 5.3. The pleated sheet arrangement. Each peptide carbonyl group is hydrogen bonded
to an N‒H hydrogen on an adjacent peptide chain.

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 (iii) β-Bends
 β-Bends (turns) connect different peptide segments forming a compact and
globular shape.
 They are generally composed of four amino acids, one of which may be proline-
imino acid that causes a "kink" in the polypeptide chain. Glycine, the amino acid
with the smallest R-group, is also frequently found in β-bends.

Figure 5.4. A β-turn that links two segments of antiparallel β‒sheet. The dotted line indicates
the hydrogen bond between the first and fourth amino acids of the four-residue segment Ala-
Gly-Asp-Ser.

C) Tertiary structure:
Tertiary structure of a protein refers to its overall three-dimensional, folded and
biologically active conformation.
Polypeptides with more than a few hundred amino acid residues often fold into two
or more stable, globular units called domains.
It consists of regions of α-helices, β-pleated sheets, and β-turns conformations.
The tertiary structure of a protein is stabilized by the following interactions:
 Hydrophobic interactions: They occur between the non-polar side chains of
neutral amino acids
 Electrostatic bonds: These bonds are formed between oppositely charged
groups of amino acid side chains.
 Hydrogen bonds: Amino acid side chains are involved in the hydrogen bond
formation. Hydroxyl group of serine, threonine, the amino groups and carbonyl
oxygen of glutamine and aspargine.
 Disulfide bonds: they occur between two cysteine residues (—S—S—).

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 (a) (b) (c) (d) (e)

Figure 5.5. Interactions that contribute to stabilizing the tertiary and

quaternary structures of proteins: (a) hydrogen bonding, (b) ionic bonding (electrostatic
interaction), (c) hydrophobic interaction, and (d) ionic bonding (e) disulfide bridge.

Figure 5.6. The tertiary structure of a typical globular protein includes segments of α-helix
with segments of random coil

D) Quaternary structure:
Quaternary structure refers to the association of two or more peptide chains in
the complete protein that are held together by different types of interactions (same
interactions as for tertiary structure). Not all proteins have quaternary structure.
In general, most proteins larger than 50 kDa consist of more than one chain.
For example, hemoglobin, the oxygen carrier in mammalian blood, consists of four
peptide chains fitted together to form a globular protein.

Figure 5.7. A schematic representation of quaternary

structure.

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