SECONDARY AND TERTIARY STRUCTURES OF PROTEIN

MPS-301 (E) :
STRUCTURES,
PROPERTIES, AND
FUNCTIONS OF
BIOMOLECULES

BY JITESH BARMAN

DEPARTMENT OF PHYSICS, BHU DATE – 31-10-2023

 Recapitulations
➢ Building block of Protein: Amino acids

➢ Structure, properties of amino acids

➢ Peptide bond and its properties

➢ Ramachandran angles: rotation of amino acid residues peptide bond

 Structure of proteins
➢ Proteins are divided at four levels depending upon the hierarchy of
their organizations
 Primary structure of protein
➢ Proteins are divided at four levels depending upon the hierarchy of
their organisations
 Secondary structure of Proteins
➢ The repetitive patterns of phi and psi angles of the polypeptide

backbone define what is known as secondary structure

➢ The classical regular secondary structure elements frequently found in

proteins are the α-helix, β-strand, and the reverse turns, in addition to

loop regions characterized by the lack of a repetitive pattern

 α- Helix structure of Proteins
➢ The α-helix was predicted by Linus
Pauling based on the known chemical
structure of polypeptides, including the
fact that the peptide bond is planar and
the C–N distance within this bond is
1.32Å
➢ The α-helices found in proteins are
righthanded
➢ Maximize the noncovalent interactions
i.e. the Hydrogen bonds
➢ The α-helix has 3.6 residues per turn,
and the hydrogen bonds are formed
between C’=O of one residue and N–H of
another residue
➢ Skipping three positions: C’=O of residue
1 pairs with N–H of residue 5, residue 2
with 6, and so on.
➢ Pitch is 5.4 angstrom
➢ Phi ~ 57 deg, and psi ~ 47 deg falls
within the Ramachandran plot.
α- Helix structure of Proteins
 Different Helix structure of Proteins
➢ There are other possible helical elements of secondary structure in
proteins which are, however, very rare and energetically unfavourable
 Different Helix structure of Proteins
➢ There are other possible helical elements of secondary structure in
proteins which are, however, very rare and energetically unfavourable
 Different Helix structure of Proteins
➢ Why α−helix are abundant in protein?
β – sheet structure of Proteins
β – sheet structure of Proteins
 Examples of α- helix and β- sheets

➢ Long side chains, such as those of Leu, Met, Gln, are frequently found in
α-helices
➢ Branched-chain amino acids (Val, Ile) and bulky side chains like Trp, Tyr,
and Phe are usually found in β-sheets
➢ Proline and glycine have a strong preference for turns because of their
unique conformations
Characteristics of Amino Acids
 Turn and Loops structure of Proteins
➢ Loop regions are stretches of irregular structure connecting helices,
sheets, and other regular elements
➢ They are usually localized at the surface of proteins
➢ These regions are amenable to accommodate changes than regular
secondary structure elements
➢ Loops are also functionally important elements in active sites of enzymes,
antigen-binding sites of antibodies, and in protein–protein and protein–
small molecule interfaces
➢ Charged and polar residues are common in loops, and both their side
chains and main chains (C’=O and NH groups) are involved in hydrogen
bonding with solvent or ligands
➢ The length of loops in proteins is variable, ranging from two to around 20
residues in the majority of proteins
➢ Long loops account for a protein’s mobility, as their irregular structure
allows them to adopt variable conformations, sometimes in a regulated
fashion responding to stimuli
➢ Hairpin loops are short loops connecting adjacent antiparallel β-strands
➢ Turns are also considered to be a special type of short loop with defined
characteristics
 Tertiary structure of proteins
➢ Protein tertiary structure is the three dimensional shape of a protein,
consisting only one polypeptide chain.
➢ Protein tertiary structure is very The Structure of
important from the structural and Myoglobin
functional point of view
➢ Tertiary structure play a decisive role
for
• Binging sites of ligands (protein-
drug interactions)
• Active sites of an enzymes
• Binding sites for other proteins
(protein-protein interactions)
➢ Spatial folding of any protein is
required to understand , in addition to
the former biological phenomena, how
the particular mutations or variations
in the gene that encodes a particular
protein lead to changes in the
protein’s behavior.
 Tertiary structure of proteins
➢ The unique folding of a protein is the result of non-bonded interactions
between polypeptide backbone and the side chains, acting co-operatively
➢ These non-bonded interactions which stabilise the proper folding of the
macromolecules
• Ionic (Salt birdge) and dipole-dipole
• Van der Waals and hydrophobic interactions
• Hydrogen bonds
 Ionic (salt bridge) in macromolecules
➢ Madelung equation for binding energy
2
=− + (− ) where and are empirical parameters
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 Dipole-dipole interactions
➢ van der Waals interactions are dipole-dipole, dipole-induced dipole and
London interactions
➢ Average energy of interaction of permanent dipoles can induce dipole
moments by Keesom equation
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 Dipole-induced dipole interactions
➢ Induced dipole moment =
➢ Energy of interaction is given by the Debye equation
2
2
=− 6
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 Induced dipole-induced dipole interactions
2
3
➢ London equation =− , where is the first ionization potential
4 6
➢ Lennard-Jones Potential
=− 6
+ 12
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 In next class
➢ Hydrophobic interactions, water and its properties, hydration shell

➢ The Quaternary structure of proteins

➢ Protein classes

➢ Fibrous protein, Globular proteins and other classes of proteins

 Thank you

Namaskaar !!