What are proteins?

Proteins are macromolecules

composed of amino acids linked
together through peptide bonds.

How are about proteins?

the most widely distributed

biomolecules

the most abundant biomolecules

(45% of human body)
the most complex biomolecules
the most diversified biological
functions

Proteins
Most structurally & functionally diverse group
Function: involved in almost everything

enzymes (pepsin, DNA polymerase)

structure (keratin, collagen)
carriers & transport (hemoglobin, aquaporin)
cell communication
signals(insulin & other hormones)
receptors
defense (antibodies)
movement (actin& myosin)
storage (bean seed proteins)

1.1 Amino Acids

The basic building blocks of proteins

About 300 types of AAs in nature, but

only 20 types are used for protein
synthesis in biological systems.
An amino group, a carboxyl group, a H
atom and a R group are connected to
a C atom.
The C atom is an optically active
center.

L-Amino acid

+
-

H3N

OOC
C

Amino acids
Structure
central carbon
amino group
carboxyl group (acid)
R group (side chain)

H O
H
| ||
N C COH
|
H
R

variable group
There are only 20 different amino
acids but they can be joined together
different for each amino acid in many different combinations to
form the diverse range of proteins that
confers unique chemical
exist on this planet
properties to each amino acid
like 20 different letters of an alphabet
can make many words (proteins)

1.1.a Classification
The R groups, also called side chains,
make each AA unique and distinctive.
R groups are different in their size,
charge, hydrogen bonding capability
and chemical reactivity.
Aas are grouped as (1) non-polar,
hydrophobic; (2) polar, neutral; (3)
basic; and (4) acidic.

Non-polar and hydrophobic AAs

R groups are non-polar, hydrophobic
aliphatic or aromatic groups.
R groups are uncharged.
AAs are insoluble in H2O.

TYPES OF AMINO ACIDS

Equal number of amino and carboxyl groups
makes it neutral; more
number of amino than carboxyl groups makes
it basic and more
carboxyl groups as compared to amino groups
makes it acidic.

Basic AAs
R groups have one -NH2.
R groups are positively charged at
neutral pH (=7.0).
AAs are highly hydrophilic.

Acidic AAs
R groups have COOH.
R groups are negatively charged at
physiological pH (=7.4).
AAs are soluble in H2O.

Aspartic acid
(Asp or D)

glutamic acid
(Glu or E)

The amino acids, which can be synthesised in

the body, are known as nonessential
amino acids.1. Glycine,2. Alanine
3.Glutamic acid 4.Aspartic acid
5.Glutamine
On the other hand, those which cannot be
synthesised in the body and must be obtained
through diet, are known
as essential amino acids .
Valine* Leucine*
Isoleucine*Arginine*Lysine*

Zwitter Ion
Amino acids are usually colourless, crystalline solids. These are water-soluble,
high melting solids and behave like salts rather than simple amines or
carboxylic acids. This behaviour is due to the presence of both acidic (carboxyl
group) and basic (amino group) groups in the same molecule.
In aqueous solution, the carboxyl group can lose a proton and amino group
can accept a proton, giving rise to a dipolar ion known as zwitter ion. This
isneutral but contains both positive and negative
charges.
In zwitter ionic form, amino acids show amphoteric behaviour as
they react both with acids and bases.
Except glycine, all other naturally occurring -amino

Amphoteric Nature
In zwitter ionic form, amino acids show amphoteric behaviour
as they react both with acids and bases.

Isoelectric point

AAs in solution at certain pH are predominantly in

dipolar form, fully ionized but without net charge
due to -COO- and -NH3+ groups.
This characteristic pH is called isoelectric point,
designated as pI.
pI is determined by pK, the ionization constant of the
ionizable groups.

R CH COOH
NH2

R CH COOH
NH3+

+OH

+H+

R CH COONH3

+OH

+H+

R CH COONH2

pH<pI

pH=pI

pH>pI

cation

amphoteric

anion

Peptides
A Peptide and peptide bond
A peptide bond is a covalent bond
formed between the carboxyl group of
one AA and the amino group of its next
AA with the elimination of one H2O
molecule.

Peptides can be extended by adding

multiple AAs through multiple peptide
bonds in a sequential order.
dipeptide, tripeptide, oligopeptide, polypeptide

AAs in peptides are called as residues.

2.1 Primary Structure

The primary structure of proteins is defined as
a linear connection of AAs along the protein
chain. It is also called amino acid sequence.
The AA sequence must be written from the Nterminus to the C-terminus.
Peptide bonds are responsible for maintaining
the primary structure.

Sickle cell anemia

Hb A :
Val-His-Leu-Thr-Pro-Glu-Glu-LysHb S : Val-His-Leu-Thr-Pro-Val -GluLys-

Sickle cell anemia

Im
hydrophilic!

Just 1
out of 146
amino acids!

But Im
hydrophobic!

2.2 Secondary Structure

The secondary structure of a protein is defined
as a local spatial structure of a certain peptide
segment, that is, the relative positions of
backbone atoms of this peptide segment.

Secondary structure of protein

The secondary structure of protein refers to the
shape in which a long polypeptide chain can
exist.
These structures arise due to the regular folding
of the backbone of the polypeptide chain due to
hydrogen bonding between C = O and
NH groups of the peptide bond.

Repeating units of N(-H), C, and C(=O)

constitute the backbone.

H-bonds are responsible for stabilizing the

secondary structure.
The side chains are not considered.
-helix
-pleated sheet

2.2.a -helix
A helical conformation is right-handed.
3.6 AAs per turn and a 0.15 nm vertical
distance, creating a pitch of 0.54 nm.
Side chains of AA residues protrude
outward from the helical backbone.

The hydrogen-bonds are parallel to the

helical axis.

Left-hand versus right-hand

0.54 nm
3.6

C
O
N

n3H

nO

0.5 nm

The -CO group of residue n is H-bonded to the NH group of residue (n+4).

-pleated sheet

An extended zigzag conformation of

protein backbones
Protein backbones are arranged sideby-side through H-bonds.
H-bonds are perpendicular to the
backbone direction.

The side chains of adjacent AAs

protrude in opposite directions.
The adjacent protein backbones can
be either parallel or anti-parallel.

2.3 Tertiary Structure

The tertiary structure is defined as the spatial

positions of all atoms of a protein, i.e., the
three-dimensional (3D) arrangement of all
atoms.

Four types of interactions stabilize the

protein tertiary structure.
hydrophobic interaction
ionic interaction
hydrogen bond
van der Waals interaction

2.4 Quaternary Structure

The quaternary structure is defined as
the spatial arrangement of multiple
subunits of a protein.

 Proteins need to have two or more

polypeptide chains to function properly.

Each individual peptide is called

subunit.
These subunits are associated through
H-bonds, ionic interactions, and
hydrophobic interactions.
Polypeptide chains can be in dimer,
trimer .., as well as homo- or heteroform.

From primary to quaternary structure

Fibrous proteins
Fibrous proteins
When the polypeptide chains run parallel and
are held together by hydrogen and disulphide
bonds, then fibre like structure is formed.
Such proteins are generally insoluble in water.
Some common examples are
keratin (present in hair, wool, silk) and myosin
(present in muscles), etc.

Globular proteins
Globular proteins
This structure results when the chains of
polypeptides coil around to give a spherical
shape. These are usually soluble in water.
Insulin and albumins are the common
examples of globular proteins.

Protein denaturation
Unfolding a protein
conditions that disrupt H bonds, ionic bonds,
disulfide bridges
temperature
pH
salinity

alter 2 & 3 structure

alter 3-D shape

destroys functionality
some proteins can return to their functional shape after
denaturation, many cannot

Protein denaturation
The process in which a protein loses its native
conformation under the treatment of
denaturants is referred to as protein
denaturation.
The denatured proteins tend to
- decrease in solubility;
- increase the viscosity;
- lose the biological activity;
- lose crystalizability;
- be susceptible to enzymatic digestion.

 Denaturants
physical: heat, ultraviolet light, violent shaking,
chemical: strong acids, bases, organic solvents,
detergents.
During denaturation 2 and 3 structures are
destroyed but 1 structure remains intact.
Common examples of denaturationThe coagulation of egg white on boiling

Curdling of milk which is caused due to the

formation of lactic acid by the bacteria present in
milk.