Chemistry of Proteins (Part - III) Structural organization of proteins

1. 1 of 37Ashok KattaStructural Organization of
Proteins

2. 2 of 37Ashok KattaStructural Organization of
Proteins
Every protein in its native state has a
unique 3D structure.
And is referred to as its conformation.
All these proteins are made up of only 20
AAs.
The number & sequence of these AAs are
different in different proteins.
The function of the protein arises from its
conformation. i.e its 3D structure.

3. 3 of 37Ashok KattaStructural Organization of
Proteins
Primary
structure
Secondary
structure
Tertiary
structure
Quaternary
structure

4. 4 of 37Ashok KattaStructural Organization of
Proteins
This is refers to the number and sequence of
AAs and location of disulfide bond in
proteins.
It largely responsible for its functions
Proteins have unique AA sequences
specified by genes.

5. 5 of 37Ashok KattaStructural Organization of
Proteins
In protein, AAs are held together by covalent peptide
bonds.
Linkage of many AAs through peptide bonds results in an
unbranched chain called polypeptide
Each polypeptide chain is having free amino group at one
end called N-terminal and free carboxyl group at another
end, called C-terminal.
The amino acids sequences are read from N-terminal to C-
terminal ends of the peptide.

6. 6 of 37Ashok KattaStructural Organization of
Proteins
Primary structure of insulin
Two peptides of 21 and 30 AAs
Two inter-chain -S-S- bonds
One intra-chain -S-S- bond

7. 7 of 37Ashok KattaStructural Organization of
Proteins
Clinical Importance of Primary
Structure
Understanding of primary structure of a protein is
important because
Majority of genetic disorders are due to abnormalities in
the AA sequences of the proteins.
If the primary structure of the normal and mutated
proteins are known, this information may be used to
diagnose or study the disease.

8. 8 of 37Ashok KattaStructural Organization of
Proteins
For stability of primary structure hydrogen bonding
between the H of NH and O of C=O groups within the
polypeptide chain takes place.
This gives rises to folding and twisting of the primary
structure.
Thus, regular folding and twisting of the polypeptide
chain by hydrogen bonds is called secondary structure of
protein.

9. 9 of 37Ashok KattaStructural Organization of
Proteins
There are two main regular forms of secondary
structure:
α-helix
β-pleated sheets,
–other forms may be found.
• β-bend or β-turn
• Triple helix
• Loop regions

10. 10 of 37Ashok KattaStructural Organization of
Proteins
It is a right handed spiral
structure
If a backbone of polypeptide
chain is twisted by an equal
amounts about each α-carbon, it
forms a coil or helix.
The helix is stabilized by
hydrogen bonds beween the NH
and CO groups of the same chain.

12. 12 of 37Ashok KattaStructural Organization of
Proteins
All peptide bonds except 1st &
last in polypeptide chain,
participate in hydrogen bonding.
Glycine and proline are
destabilizes α-helix.

13. Left-hand versus right-hand

14. 14 of 37Ashok KattaStructural Organization of
Proteins

15. 15 of 37Ashok KattaStructural Organization of
Proteins

16. 16 of 37Ashok KattaStructural Organization of
Proteins
This is another form of secondary
structure
The surfaces of β-sheets appear
“pleated,” and these structures are,
therefore, often called “β-pleated sheets.”
A polypeptide chain in the β-pleated
sheet is almost fully extended rather than
being tightly coiled as in the α-helix.

17. 17 of 37Ashok KattaStructural Organization of
Proteins
Unlike α-helix, β-sheets are
composed of two or more
polypeptide chain.
It also stabilized by H bonding
between different or same
polypeptide chains.
In β-sheet, the H bonds are
perpendicular to the polypeptide
rather than parallel as in the α-
helixes.

18. 18 of 37Ashok KattaStructural Organization of
Proteins
A β-sheet can be formed from
two or more separate polypeptide
chains or segments of
polypeptide chains that are
arranged
–either antiparallel to each other.
OR
–parallel to each other

19. The three dimensional (3D) folded compact and biologically
active conformation of a protein is referred to as its tertiary
structure.

20. 20 of 37Ashok KattaStructural Organization of
Proteins
Secondary structure, may be further folded and twisted
about itself forming three-dimensional arrangement of
the polypeptide chain
AA which are very distant from one another in the
sequence can be drought very near due to folding
Thus form regions essential for the functioning of the
protein, like active site or catalytic site of enzymes.

21. 21 of 37Ashok KattaStructural Organization of
Proteins
The three-dimensional tertiary structure of a
protein is stabilized by:
Hydrogen bonds
Hydrophobic interactions
Van der Waals forces
Disulfide bond
Ionic (electrostatic) bonds or salt bridges.

22. 22 of 37Ashok KattaStructural Organization of
Proteins
Myoglobin (Mb)
Located in muscle to supply O2
1st protein in high resolution
153 AAs
75% of structure is -helix in 8
regions.
The interior almost entirely
nonpolar residues

23. 23 of 37Ashok KattaStructural Organization of
Proteins
Domains
Domains are the functional and three-dimensional
structural units of a polypeptide.
As an example, an enzyme has different domains, a
domain that functions as catalytic site, another
domain that functions as an allosteric site.

24. 24 of 37Ashok KattaStructural Organization of
Proteins
Many proteins consist of a single polypeptide
chain, and are defined as monomeric proteins.
Example - myoglobin
However, others may consist of two or more
polypeptide chains that may be structurally identical
or totally unrelated.
The arrangement of these polypeptide subunits
is called the quaternary structure of the protein.

25. 25 of 37Ashok KattaStructural Organization of
Proteins
Subunits may either function independently of
each other, or may work cooperatively, as in
hemoglobin
Subunits are held together by noncovalent
interactions
hydrogen bonds,
ionic bonds, and
Hydrophobic interaction
Example- Haemoglobin, Creatinine Kinase.

26. 26 of 37Ashok KattaStructural Organization of
Proteins
Hemoglobin(Hb)
O2 transporter in erythrocyte
Mead up of…
2  subunits, 141 AAs
2  subunits, 146 AAs
4 subunits are maintained together
by 8 pairs of ionic interactions.
Each subunit contains one heme
group.
The conserved hydrophobic core
stabilizes the 3D structure.

28. 28 of 37Ashok KattaStructural Organization of
Proteins
From primary to quaternary structure
Four Level of Structure of Protein…

29. 29 of 37Ashok KattaStructural Organization of
Proteins
Protein structure is stabilized by two type of bonds.
Covalent bond,
• Peptide bond
• Disulfide bond and
Non-covalent bond,
• Hydrogen bond
• Hydrophobic bond or interaction
• Ionic or electrostatic bond
• Van der Waals interactions.

30. NH2 COOH1 NH2 COOH2
NH2 C N COOH
O
H
21
Amino acids are connected head to tail
Dehydration
H2O

31. 31 of 37Ashok KattaStructural Organization of
Proteins
This is a rigid bond, strong, no rotation
of protein molecule can occur around this
bond, so it stabilizes the protein
structure.
Peptide bonds cannot broken by
denaturation.
They can be broken by enzymatic
action or by strong acid or base at
elevated temperature.

32. 32 of 37Ashok KattaStructural Organization of
Proteins
Disulfide bond between 2
cysteine residues in same
polypeptide chain or different
polypeptide chains.
It is a very stable bond resists
conditions usual for protein
denaturation.

34.  Bond formed between -NH and -CO groups of peptide
bond by sharing single hydrogen.
 It may occur within intrachain or Interchain
 Side chains (R groups) of 11 out of the 20 standard AAs can
also participate in “H” bonding.

35. 35 of 37Ashok KattaStructural Organization of
Proteins
 Formed by interaction between
nonpolar hydrophobic R groups of
AAs
 Alanine, valine, leucine, isoleucine,
methionine, phenylalanine and
tryptophan.
 They are not true bonds but
interactions that help to stabilize
the protein structure.

36. 36 of 37Ashok KattaStructural Organization of
Proteins
These bonds occur between the
charged group of side chains of
amino acids.
 (NH3+ of basic AAs & COO-- of
acidic AAs)

37. 37 of 37
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