Protein & its

Structure

Sayema Khanum
Assistant Professor
Department of Pharmacy,
Jagannath University
Importance of Proteins
Main catalysts in biochemistry: enzymes (involved
in virtually every biochemical reaction)
Structural components of cells (both inside and
outside of cells in tissues)
Regulatory functions (if/when a cell divides, which
genes are expressed, etc.)
Carrier and transport functions (ions, small
molecules)
Structure of an Amino
Acid
Structure of an Amino
Acid
Amino acids have an amino group and a carboxyl
group
Both groups are covalently bonded to the center
carbon atom, called the alpha carbon.
Bonded to the alpha carbon is a hydrogen atom
and a chemical group called the ‘R group’.
The amino acid type differs depending on the
structure of the R group.
The 20 Amino Acids Found in
Proteins
Peptide bond
1. When the carboxyl
group of one amino
acid molecule reacts
with the amino
group of the other
amino acid molecule,
causing the release
of a molecule of
water, a peptide
bond is formed
2. In a polypeptide
chain many amino
acids are bonded by
peptide bond. Each
amino acid is called Figure-Peptide bond
is residue.
3. Regular repeating
part of the chain is
called the main
chain(backbone) and
the variable part is
called the side chain.
4. Polypeptide chain
contains:-1. 50-2000
residue 2. 5500-
220000 molecular
weight. Figure-Polypeptide
Condensation Reactions
A chemical reaction in which two molecules
become covalently bonded to each other
through the loss of a molecule, usually water.
When a bond forms between two monomers
(amino acids), making a Dipeptide, each
monomer contributes to the lost water
molecule.
Cells must expend energy to carry out
dehydration synthesis.
This process results in the formation of a
Peptide bond, which can be joined with other
bonds that will eventually contribute to the
formation of a larger molecule (Polypeptide
chain or Protein).
Primary Structure of
Proteins
The primary structure of peptides and proteins
refers to the linear number and order of the amino
acids present.
The convention for the designation of the order of
amino acids is that:
The N-terminal end (i.e. the end bearing the
residue with the free α-amino group) is to the left
(and the number 1 amino acid) and the C-terminal
end (i.e. the end with the residue containing a free
α-carboxyl group) is to the right
Peptide bond
is rigid and
planner why?
1. The bond between
carbonyl carbon and
nitrogen atom is not
pure single bond. It is a
partial double bond.So
it is not free to rotate.
2. The length of this bond
is 1.32 angstrom which Figure-Polypeptide
is between that of a C-
N single bond is 1.49
angstrom and C=N
double bond is 1.27
angstrom. The bond
between α carbon atom
and carbonyl carbon
atom is a pure single
bond.α-carbon and
Nitrogen atom is also a
pure single bond. Both
the bonds are free to
rotate on either side of
rigid peptide bond.
3. The rigidity enables Figure-The peptide unit is rigid planer
protein to have well array of four atoms(N,H,C and O)
defined 3D structure.
Freedom rotation helps
protein to fold in many
It is the partial double-bond character of the peptide bond that
defines the conformations a polypeptide chain may assume.

The bond is planar, and the group can take one of two major
configurations:

is or Trans

CIS TRANS
CONFIG CONFIG
The cis configuration of the peptide group has a much
greater steric hindrance between the two amino
acids. This means that the atoms get in the way of
each other.
For this reason nearly all of the peptide bonds in
naturally occurring proteins are in the trans
configuration, at the very least 95% of them are
trans-peptide bonds.
Disulfide bond
and Importance
of disulfide bond
Disulfide bond:-
Disulfide bond is a
covalent cross linked
bond between two
polypeptide chains by
the oxidation of cysteine
residue . The product is
called cystine.
Importance of
disulfide bond
1.It is responsible for
three dimensional
structure of protein .
2. Prevent them from
being denatured in the
extracellular
environment . Thus
helps protein to continue Cysteine
their normal
physiological function. Cystine
Structures of Protein
α-helix in protein
structure

1. The α-helix is a rod like

structure. The carbonyl
group of residue n is H-
bonded to the NH group
of residue and (n+4) in
the same standard.
2. The polypeptide is Figure-Polypeptide
tightly coiled. It forms
the inner part of the rod
and the side chain
extend outwards. Alpha helix
3. Each residue is related
to the next one by rise
of 1.5 angstrom along
the helix axis and a
rotation of 100 degree
which keeps 3.6 amino
acid per turn of helix.
4. Protein may contain 0-
100 % α-helix. Example-
Chymotrypsin is
virtually devoid of α-
helix where as 75%
β pleated β pleated sheets
sheets in
protein
structure
1. It is almost fully
extended.
2. The axial distance
between adjacent
amino acid along a
β-strand
approximately is
3.6 angstrom.
3. β-pleated sheet is
stabilized by
hydrogen bonds
between NH and
CO in different
polypeptide
strands.
4. Adjacent chains in
a β-pleated sheet
in the same
direction or in the
opposite direction.
Example:-Silk fiber
(antiparallel).
β-Sheets

Unlike the compact backbone of the α helix, the peptide

backbone of the β sheet is highly extended.
β-sheets are said to be pleated in which the R groups of
adjacent residues point in opposite directions.

β-sheets are either parallel or antiparallel.

In parallel sheets adjacent peptide chains proceed
in the same direction (i.e. the direction of N-
terminal to C-terminal ends is the same).

In antiparallel sheets adjacent chains are aligned

in opposite directions.
β-Bends & Loops
Roughly half of the residues in a “typical” globular
protein reside in α helices and β sheets

and half in loops,turns, bends, and other extended

conformational features.

Turns and bends refer to short segments of amino

acids that join two units of secondary structure,
such as two adjacent strands of an antiparallel β
sheet.
Tertiary Structure of
Proteins
Tertiary structure refers to the complete three-
dimensional structure of the polypeptide units of a
given protein.
Secondary structures of proteins often constitute
distinct domains.
Domain is the basic unit of structure and function
Tertiary structure describes the relationship of
different domains to one another within a protein.
OR the final arrangement of domains in a
polypeptide.
The interactions of different domains is governed
by several forces:

These include-
hydrogen bonding,
hydrophobic interactions,
 electrostatic interactions and
van der Waals forces.

A- helix and B- sheet --- hydrogen bonding and this

eliminates the possibility of water to disrupt the
structure of proteins.
Forces Controlling
tertiary Structure
Hydrogen Bonding:
Polypeptides contain numerous proton donors and
acceptors both in their backbone and in the R-
groups of the amino acids.
The environment in which proteins are found also
contains the H-bond donors and acceptors of the
water molecule.
H-bonding, occurs not only within and between
polypeptide chains but with the surrounding
aqueous medium.
Hydrophobic Forces:
•Proteins are composed of amino acids that contain
either hydrophilic or hydrophobic R-groups.
•It is the nature of the interaction of the different R-
groups with the aqueous environment that plays
the major role in shaping protein structure.
•The spontaneous folded state of globular proteins
is a balance between the opposing energetics of H-
bonding between hydrophilic R-groups and the
aqueous environment and the repulsion from the
aqueous environment by the hydrophobic R-groups.
•The hydrophobicity of certain amino acid R-groups
tends to drive them away from the exterior of
proteins and into the interior. This driving force
restricts the available conformations into which a
protein may fold.
Electrostatic Forces:
Electrostatic forces are mainly of three types;
charge-charge, charge-dipole and dipole-dipole.
Typical charge-charge interactions that favor
protein folding are those between oppositely
charged R-groups such as K or R and D or E.
Charge-dipole interactions:
This refers to the interaction of ionized R-groups
of amino acids with the dipole of the water
molecule.
Van der Waals Forces:
There are both attractive and repulsive van der
Waals forces that control protein folding. Attractive
van der Waals forces involve the interactions among
induced dipoles that arise from fluctuations in the
charge densities that occur between adjacent
uncharged non-bonded atoms.
Repulsive van der Waals forces involve the
interactions that occur when uncharged non-bonded
atoms come very close together. The repulsion is the
result of the electron-electron repulsion that occurs
as two clouds of electrons begin to overlap.
Van der Waals forces are extremely weak, relative to
other forces, it is the huge number of such
interactions that occur in large protein molecules
that make them significant to the folding of proteins.
Quaternary Structure
Many proteins contain 2 or more different
polypeptide chains that are held in association by
the same non-covalent forces that stabilize the
tertiary structures of proteins.
The arrangement of these polypeptide subunits
is called the quaternary structure of proteins.
Two subunits- dimeric

Three subunits- trimeric

Proteins with multiple polypetide subunits are

oligomeric proteins.
Oligomeric proteins can be composed of multiple identical
polypeptide chains or multiple distinct polypeptide chains.
Proteins with identical subunits are termed homo-
oligomers.
Proteins containing several distinct polypeptide chains
are termed hetero-oligomers.
Hemoglobin, the oxygen carrying protein of the blood,
contains two α and two β subunits arranged with a
quaternary structure in the form, α2β2.

Hemoglobin is, therefore, a hetero-oligomeric protein.

Structure of
Haemoglobin
 Denaturation De-naturation and Re-
and naturation of protein
Renaturation
of protein
Denaturation:
Denaturation of protein means
destruction of three dimensional
structure of native protein or wild
protein. The reasons for the 3d
structure are disulfide bond and
hydrophobic interaction.
Native protein can be converted into a
denatured protein by the cleavage of
disulfide bond present in it. For
example: Ribonuclease. A single
polypeptide chain consisting of 124
amino acid , it has four disulfied bond
which can be cleaved reversibly by
reducing them with reducing agent.
Reducing agent used for disulphide
bond-
1)β – merceptoethanol.
2)Urea.
3)Guanidine hydrochloride.
Renaturation:
The conversion of de-naturated protein
into native protein is called re-
naturation of protein.
Thank You