1.
 Proteins are the most abundant organic
molecules of the living system.
 They constitute about 50% of the cellular dry
weight.
 They constitute the fundamental basis of
structure and function of life.
 In 1839, Dutch chemist G.J. Mulder was first to
describe about proteins.
 The term protein is derived from a Greek word
proteios, meaning first place.
 The proteins are nitrogenous macromolecules
that are composed of many aminoacids.

2.
 Amino acids are a group of
organic compounds containing
two functional groups – amino
and carboxyl.
 The amino group[ -NH2] is basic
while the carboxyl group [-
COOH] is acidic in nature.
 There are about 300 aminocids
occur in nature. Only 20 of them
occur in proteins.

3.
 Each amino acid has 4 different groups attatched to α-
carbon ( which is C atom next to COOH).These 4 groups
are : amino group, COOH group , Hydrogen atom and
side chain(R).

4.
 α- carboxyl group of one amino acid
(with side chain R1) forms a covalent
peptide bond with α- amino group of
another amino acid (with side chain R2)
by removal of a molecule of water.
 The result is : Dipeptide.
 The dipeptide can then form a second
peptide bond with a third amino acid(
with side chain R3) to give tripeptide.
 Repetition of this process generates a
polypeptide or protein of specific
aminoacid sequence.
 Has 40% double bond character, caused
by resonance.

5.
 Polypeptide backbone is the
repeating sequence of the N-C-
C-N-C-C… in the peptide bond.
 The side chain or R group is not
part of the backbone or the
peptide bond.

6.
• Configuration : geometric relationship between a given
set of atoms.
Ex: that distinguish L-amino acid from
D-amino acid.
• Conformation : spatial arrangement of atoms in a
protein.
• Thermodynamically the most stable conformations exist.
• Stabilized largely by weak interactions.

7.
• Stability - tendency to maintain a
native conformation.
• Native conformation stabilized by:
Disulphide bonds
Non covalent forces

8.
Proteins have different levels of organisation
 Primary Structure
Secondary Structure
Tertiary Structure
Quaternary Structure

9.
Primary structure - determined by
covalent bonds
Secondary, Tertiary,
Quaternary structure - determined by
weak forces

10.
Primary
Secondary
Tertiary
Quaternary
Assembly
Folding
Packing
Interaction

11.
 The primary structure of protein refers to
the sequence of amino acids present in the
polypeptide chain.
 Amino acids are covalently linked by
peptide bonds or covalent bonds.
 Each component amino acid in a
polypeptide is called a "residue” or
“moiety”.
 By convention the primary structure of
protein starts from the amino terminal (N)
end and ends in the carboxyl terminal (C)
end.

12.
 It is a local, regularly
occurring structure in proteins
and is mainly formed through
hydrogen bonds between
backbone atoms.
Pauling & Corey studied the
secondary structures and
proposed 2 conformations
o α helix
o β sheets.

13.
 Right handed spiral structure.
 Side chain extend outwards.
 Stabilized by H bonding that are
arranged such that the peptide Carbonyl
oxygen (nth residue) and amide
hydrogen(n+4 th residue).
 Amino acids per turn – 3.6
 Pitch is 5.4 A°
 Alpha helical segments, are found in
many globular proteins like
myoglobin,troponin C.
 Length ~12 residues and ~3 helical
turns.
 phi = -60 degrees, psi = -45 degrees ,
falls within the fully allowed regions of
the Ramachandran diagram.

14.
α-helix
Also called the 3.612
π-helix
Very loosely coiled H-
bonding pattern n + 5
Rarely found in nature.
310-helix
Very tightly coiled H-
bonding pattern n+3 rarely
found in nature

15.
o Formed when 2 or more
polypeptides line up side by
side.
o Individual polypeptide –
beta strand.
o Each beta strand is fully
extended.
o They are stabilized by
hydrogen bond between N-
H and carbonyl groups of
adjacent chains.

16.
o Beta sheets come in two varieties
Antiparallel beta sheet – neighboring hydrogen bonded
polypeptide chains run in opposite
direction.
Parallel beta sheet - hydrogen bonded chains extend in
the same direction.
The connection between two antiparallel strands may be just a small loop but the
link between tandem parallel strands must be a crossover connection that is out of
the plane of the β sheet.

17.
The two major sorts of
connection between β strands:
 a hairpin or same end
connection
 a crossover or opposite end
connection.

18.
It is the angle between
two intersecting
planes.
It helps to maintain
the protein structure.

19.
 The backbone or main chain of a protein
refers to the atoms that participate in
peptide bonds, ignoring the side chains of
the aminoacid residues.
 The only reasonable free movements are
rotations around the Cα – N
bond(measured as Φ) and the Cα –C
bond ( measured as Ψ).
 These angles are both defined as 180°
when the polypeptide chain is in full
conformation.
 The conformation of the backbone can
therefore be described by the torsion
angles ( also called dihedral angles or
rotational angles).

20.
 Ramachandran plot – to visualize the
backbone of aminoacid residues.
 The aminoacids with larger side
chains will show less number of
allowed region within the
ramachandran plot.

21.
 A Ramachandran plot is a way to
visualize backbone dihedral
angles ψ against φ of amino acid
residues in protein structure.
 A Ramachandran plot can be used
to show which values, or
conformations, of the ψ and φ
angles are possible for an amino-
acid residue in a protein and to
show the empirical distribution of
datapoints observed in a single
structure.
 The darkest areas correspond to
the "core" regions representing the
most favorable combinations of
phi-psi values.

22.
o Glycine and proline has no
preffered Ramachandran
Plot.
o Glycine is formally
nonpolar, its very small side
chain makes no real
contribution to hydrophobic
interactions.
o Proline has an aliphatic side
chain with a distinctive
cyclic structure. The
secondary amino group of
proline residues is held in a
rigid conformation that
reduces the structural
flexibility of polypeptide
residues containing proline.

23.
 The peptide bond allows for
rotation around it and therefore
the protein can fold and orient the
R groups in favorable positions.
 Weak non-covalent interactions
will hold the protein in its
functional shape – these are weak
and will take many to hold the
shape.
 Protein folding occurs in the
cytosol.

24.
2 regular folding patterns have
been identified – formed between
the bonds of the peptide
backbone.
 -helix – protein turns like a
spiral – fibrous proteins (hair,
nails, horns).
 -sheet – protein folds back
on itself as in a ribbon –
globular protein.

25.
 Loops and Turns
 In addition to α helices and β strands, a folded
polypeptide chain contains two other types of
secondary structure called loops and turns.
 Loops and turns connect α helices and β strands.
 The most common types cause a change in direction of
the polypeptide chain allowing it to fold back on itself
to create a more compact structure.
 Loops have hydrophilic residues and they are found
on the surface of the protein.
 Loops that have only 4 or 5 amino acid residues are
called turns when they have internal hydrogen bonds.
 Reverse turns are a form of tight turn where the
polypeptide chain makes a 180° change in direction.
 Reverse turns are also called β turns because they
usually connect adjacent β strands in a β sheet.

26.
 Also known as beta bends or tight turns.
 In a beta turn, a tight loop is formed when the
carbonyl oxygen of one residue forms a hydrogen
bond with the amide proton of an amino acid
three residues down the chain. This hydrogen
bond stabilizes the beta bend structure.
 Proline and Glycine are frequently found in beta
turns, proline because its cyclic structure is
ideally suited for the beta turn, and glycine
because, with the smallest side chain of all the
amino acids, it is the most sterically flexible.
 A beta turn is a means by which the protein can
reverse the direction of its peptide chain.
 Beta turns often promote the formation
of antiparallel beta sheets.

27.
 The tertiary structure defines the specific overall 3-D shape
of the protein.
 Tertiary structure is based on various types of interactions
between the side-chains of the peptide chain

28.
In globular proteins
 Tertiary interactions are frequently stabilized by sequestration
of hydrophobic amino acid residues in the protein core.
 Consequent enrichment of charged or hydrophilic residues on
the protein's water-exposed surface.
In secreted proteins
 disulfide bonds between cysteine residue helps to maintain the
protein's tertiary structure

29.
Interactions stabilizing tertiary structure :
1. Disulfide bonds
2. Hydrophobic interactions
3. Hydrogen bonds
4. Ionic interactions
5. Vander Waals force

30.
Covalent bond between
sulfur atoms on two
cysteine amino acids.

31.
 H bonds are weak which
allows to be broken and
reformed easily.
 Allows structural change
and produces
‘functional’molecules

32.
• Ions on R groups form
salt bridges through
ionic bonds.
• NH3 +
and COO- areas of
the protein attract and
form ionic bonds.

33.
 Close attraction of non-polar R
groups through dispersion
forces.
 They are non attractive
interactions, but results from
the inability of water to form
hydrogen bonds with certain
side chains.
 Very weak but collective
interactions over large area
stabilize structure.
 Repel polar and charged
molecules/particles.

34.
 Globular proteins fold up into
compact, spherical shapes.
 Their functions include biosynthesis,
transport and metabolism.
 For example, myoglobin is a globular
protein that stores oxygen in the
muscles.
- myoglobin is a single peptide
chain that is mostly -helix
- the O2 binding pocket is
formed by a heme group and
specific amino acid side-chains
that are brought into position
by the tertiary structure

35.
 Fibrous proteins consist of long fibers and are
mainly structural proteins.
 For example,
-keratins are fibrous proteins that
make hair, fur, nails and skin.
- hair is made of twined fibrils,
which are braids of three -helices
(similar to the triple helix
structure of collagen)
- the -helices are held together by
disulfide bonds
-keratins are fibrous proteins found in
feathers and scales that are made up
mostly of -pleated sheets

36.
Association of secondary structures.
 1. beta sheet super secondary structure
 2.alpha helix super secondary structure
 3. mixed super secondary structure

37.
 A domain is a basic structural
unit of a protein structure
distinct from those that make up
the conformations.
 Part of protein that can fold into
a stable structure independently.
 Different domains can impart
different functions to proteins.
 Proteins can have one to many
domains depending on protein
size.

38.
 Myoglobin is a small,
monomeric protein which serves
as an intracellular oxygen
storage site.
 It is found in abundance in the
skeletal muscle of vertebrates,
and is responsible for the
characteristic red color of muscle
tissue.
 Myoglobin is closely related to
hemoglobin, which consists of
four myoglobin-like subunits
that form a tetramer and are
responsible for carrying oxygen in
blood.

39.
 The quaternary protein structure involves the
clustering of several individual peptide or protein
chains into a final specific shape.
 A variety of bonding interactions including hydrogen
bonding, salt bridges, and disulfide bonds hold the
various chains into a particular geometry.
 Two kinds of quaternary structures: both are multi-
subunit proteins.
Homodimer : association between identical
polypeptide chains.
Heterodimer : interactions between subunits of
very different structures.
 The interactions within multi subunits are the same
as that found in tertiary and secondary structures

40.
 Quaternary structure adds stability by
decreasing the surface/volume ratio of
smaller subunit
 Simplifies the construction of large
complexes – viral capsids and proteosomes

41.
Proteins cannot have inversion or mirror symmetry
because bringing the protomeres into coincidence
would require converting chiral L residues to D
residues. Thus , proteins can have only rotational
symmetry.
CYCLIC SYMMETRY
Protomeres are related by a single axis of rotation.
Objects with 2, 3, or n fold rotational axis are said
to have c2 c3 c4 symmetry respectively.

42.
 2. Dihedral
symmetry
 Dihedral symmetry, a
more complicated type
of rotational symmetry,
is generated when an
n-fold rotation axis
and a 2-fold rotation
axis intersect at right
angles.
 D2 symmetry is, by
far, the most common
type of dihedral
symmetry in proteins.

43.
o Haemoglobin is a globular
protein with 4 polypeptide
chains bonded together. It
therefore has a quartenary
structure.
o There are 4 haem groups each
contain iron.
o Each haem group can carry one
molecule of oxygen.
o The four polypeptide chain consists of
two alpha and two beta chains.

44.
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