Peptides and Proteins
A peptide consists of two or more amino
acid residues linked together by peptide
bonds.
Dipeptide: combination of 2 amino acids.
Tripeptide: 3 amino acids.
Tetrapeptide : 4 amino acids.
Oligopeptide: few amino acids (up to ten).
Polypeptide: 10-50 amino acids.
Protein : A polypeptide chain made of more than 50
amino acids.
Peptide Bond Formation
Each polypeptide has N-terminal amino acid
(with free α-amino gp) and C-terminal amino
acid (with free α-carboxylic gp).
Peptide or protein structures are written with
the N-terminal residue at the left and the C-
terminal residue at the right.
Ser-Gly-Tyr-Ala-Leu
Glutathione is an example of biologically
important peptides
Glutathione (GSH)
• It is a tripeptide formed of 3 common amino
acids; glutamate, cysteine and glycine.
• Glutathione is important as an antioxidant.
Structure of Glutathione
γ- Glutamyl cysteinyl glycine
Structure of proteins (organisation of proteins)
Proteins are high-molecular weight polypeptides.
A functional protein is not just a polypeptide
chain, but one or more polypeptides precisely
twisted, folded, and coiled into a molecule of
unique shape.
Proteins have different levels of structural
organisation; primary, secondary, tertiary and
quaternary.
Protein structure
Primary structure (Amino acid sequence)
↓
Secondary structure （ α-helix, β-sheet ）
↓
Tertiary structure （ Three-dimensional
structure formed by assembly of secondary
structures ）
↓
Quaternary structure （ Structure formed by
more than one polypeptide chains ）
Levels of structure in proteins
Primary Structure of Proteins
It refers to the Sequence, Number, Types of
amino acids in a single polypeptide chain.
Peptide bonds
Amino acids
Primary Structure
Each amino acid in protein is called a residue.
Primary structure is unique (specific) for each
protein.
Gene sequence determines amino acid sequence
(primary structure).
Primary structure also determines the location of
any disulfide bonds or bridges.
This covalent disulfide bonds may be interchain
(between different polypeptide chains in the
same protein) or intrachain (between portions of
The nonapeptides oxytocin and vasopressin have similar
primary structures.
Only the amino acids at positions 3 and 8 differ.
There is an intrachain disulfide bond between
cysteine residues in positions 1 and 6.
Intrachain disulfide
bond
Primary Structure of insulin
Insulin has two polypeptide chains; the A
chain (glycine chain) with 21 amino acids,
and B (phenylalanine chain) chain with 30
amino acids.
They are held together by a pair (two) of
interchain disulfide bond.
Primary structure determines biological
activity
Even a single amino acid change
(mutation) in the linear sequence may
have serious biological effect on the
function.
In sickle cell anemia: the 6th amino acid
(glutamic acid) in the b-chain of
hemoglobin is replaced by valine.
(a) Normal red blood cells and the primary (b) Sickled red blood cells and the primary
structure of normal hemoglobin structure of sickle-cell hemoglobin
Secondary Structure
It is the regular folding of the polypeptide
chain.
Two major types of protein fold are:
– α (alpha) helix.
– β (beta) sheet.
Secondary structures are stabilized by
hydrogen bonds.
Alpha Helix
The a-helix is right-handed or
clock-wise rod-like structure.
The helix is stabilized by
Hydrogen bonds between -C=0
Hydrogen
and -NH groups. bonds
Hydrogen bonds are running
parallel to the axis of the
helix.
These bonds are individually
weak, but they collectively
serve to stabilize the helix.
e.g. keratins of hair and skin.
b-Pleated Sheet
Zigzag-like structure.
Unlike α- helix, β-sheets may be composed of
two or more peptide chains or segments of a
polypeptide chain.
Hydrogen bonding are between the chains and
are perpendicular to the polypeptide backbone.
Side chain (R) project outward on opposite sides
of the backbone.
b- Pleated Sheets
Chapter 15 17
Antiparallel and Parallel β-Pleated Sheet
If the polypeptide chains run in opposite direction, with
the N-terminal & C-terminal ends alternating, it is an
antiparallel b-sheet.
If the polypeptide chains run in the same direction, with
the N-terminal of the b-strands together, it is a parallel
b-sheet.
A comparison between α-helix & β-Pleated Sheet
α-helix:
1. Rod like structure.
2. A single polypeptide chain or a even a segment of it may
assume this structure.
3. Stabilized by intrachain hydrogen bonds.
4. Hydrogen bonding are parallel to axis of the helix.
β-sheets:
5. Zig Zag structure.
6. Between two or more peptide chains or segments of a
polypeptide chain.
7. Stabilized by interchain or intrachain hydrogen bonds.
8. Hydrogen bonding are perpendicular to the polypeptide
back bone.
Tertiary Structure
It refers to the overall folding of a single
polypeptide chain into a three- dimensional
compact protein molecule.
It involves interactions and cross links
between R groups in different areas of the
peptide chain.
All polar groups are located on the outer
surface while non-polar ones are buried
inside, hidden from water.
Tertiary Structure
Chapter 15 21
Tertiary structure
The function of protein depends on its tertiary
structure.
In this structure, the protein becomes active as a
result of the creation of active sites.
e.g. Globular proteins as albumin, globulin,
myoglobin and many enzymes.
Cross linkages (Intermolecular Forces) that stabilize
the tertiary structure:
• Hydrogen bonding
• Ionic bonds
• Disulfide linkages
• Dispersion forces (Van Der Waal’s forces)
serine aspartic cysteine alanine
23
Glutamic lysine cysteine leucine
1. Disulfide bond:
• It is formed by the oxidation of the thiol or
sulfhydryl (–SH) groups of two cysteine residues
to yield one mole of cystine.
• Disulfide bonds are strong covalent bond that
protect protein molecule against denaturation.
2. Hydrogen bond:
• A chemical bond formed between hydrogen
atom and an electronegative atom, such as
oxygen or nitrogen.
• Hydrogen bonds are weaker than covalent and
ionic bonds.
3.Van Der Waal's forces ( Dispersion forces):
• They are mutual attraction between hydrophobic
non polar side chains of amino acids.
• These forces attract when atoms are at certain
distances from each other, and repel when atoms
approach each other more closely.
• They are present in the interior of the molecules.
4. Ionic or Electrostatic bonds (Salt bridge):
• They exist between positively charged and
negatively charged groups.
Tertiary Structure of Protein
Hydrophobi
c
interaction
Quaternary Structure
Some proteins are made of multiple similar or
dissimilar polypeptide chains (subunits or
monomers).
These subunits are united by forces other than
the covalent bonds (peptides and disulfide
bonds).
The forces that stabilize these aggregate are
mostly hydrogen bonds and ionic bonds formed
between the residues on the surface of
polypeptide chains.
Quaternary Structure of hemoglobin
Hemoglobin (blood protein involved in oxygen
transport) contains two alpha chains and two
beta chains.
Summary of Structural Levels
Summary of Structural Levels
The overall shape of proteins
1) Fibrous proteins:
• They are of long, fiber- like shapes.
• Their axial ratio (length: width) is greater than 10.
• Examples:
a-keratin: The protein of hair, wool, skin, and
nails.
Myosin: The major protein of muscle.
2) Globular proteins
• They are folded or coiled in very compact
spherical manner.
• Their axial ratio is not over 3:1 or 4:1.
• Examples: Plasma albumins and globulins
as well as insulin.
