Biomolecules
Protein Structure and
Function
Prof. Bishwajit Kundu
Kusuma School of Biological Sciences
IIT Delhi, Hauz Khas, New Delhi 110016
Proteins
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Make up about 15% of the cell
Have many functions in the cell
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Enzymes
Storage
Structural
Receptors
Motor
Signaling
Protection
Transport
Gene regulation
Special functions
https://alevelbiology.co.uk/notes/functions-of-proteins/
Proteins are made of long chain of amino acids
H2O
https://www.genome.gov/genetics-glossary/Amino-Acids
H2O
Beta barrel
HIV Capsid
Coronavirus Spike proteins (NIH)
Protein structures
Primary structure
Insulin
is simply the sequence of amino
acids in a polypeptide chain.
Eg: Insulin
Eg. Hemoglobin- normal and
sickle cell anemia form
Image: open stax biology
VAL
Secondary structure
• How the sequence is twisted or folded
• An alpha helix is coil of amino acids that are
held in place by H- bonding
• Wool is a stretchy protein that is mostly
alpha helix
• The beta pleated sheets consists of an
extended chain of amino acids
• The Beta pleated sheets are placed in space
by H-bonds between groups of adjacent
chains
• Silk is a non-stretchy protein which is mostly
beta pleated sheet.
Picture: Jung’s biology Blog
https://www.youtube.com/watch?v=KKgyhqX-dI4
Tertiary structures
• How the twisted chain is folded into a
compact structure
• Tertiary structure is held in place by Hbonding and by many forces among various
groups• Non-polar groups tend to fold to the interior
of the protein where polar groups assemble
at the periphery.
https://www.quora.com/How-is-the-tertiary-structure-of-proteinformed
Quaternary structure
• Many proteins are actually assemblies of
multiple polypeptide chains. The quaternary
structure refers to the number and
arrangement of the protein subunits with
respect to one another.
• Examples Hemoglobin, DNA polymerase,
and ion channels.
Interesting facts about proteins
• Circular/Cyclic proteins?
COOH
Knotted proteins
• Human ubiquitin C-terminal hydrolase isoform 1 (UCHL1) is 52 knotted and accounts for up to 5 percent of
soluble proteins in neurons. An unknotted version of
this molecule is implicated in Parkinson’s disease.
Pawel Dabrowski-Tumanskia and Joanna I. Sulkowskaa
https://www.pnas.org/content/pnas/114/13/3415.full.pdf
Protein folding
https://www.thinglink.com/scene/971922545433378820
E
Paul M. Horowitz, Nature Biotechnology
https://www.nature.com/articles/nbt0299_136
Ken A. Dill, Justin L. MacCallum
https://science.sciencemag.org/content/338/6110/1042
Acknowledgements
Picture and content Sources
1.
Ken A. Dill, Justin L. MacCallum, https://science.sciencemag.org/content/338/6110/1042
2.
Paul M. Horowitz, Nature Biotechnology, https://www.nature.com/articles/nbt0299_136
3.
Pawel Dabrowski-Tumanskia and Joanna I. Sulkowskaa, https://www.pnas.org/content/pnas/114/13/3415.full.pdf
4.
Manueal Tarbi, David J Craik, Trends in Biochemical Sciences, https://doi.org/10.1016/S0968-0004(02)02057-1
5.
https://www.quora.com/How-is-the-tertiary-structure-of-protein-formed
6.
Picture: Jung’s biology Blog, https://www.youtube.com/watch?v=KKgyhqX-dI4
7.
Pearson Benjamin Cummings
8.
www.englishgrammerhere.com
9.
Essential Cell biology. Garland Science
10. https://www.genome.gov/genetics-glossary/Amino-Acids
11. https://alevelbiology.co.uk/notes/functions-of-proteins
Non- Covalent Bonds
Bishwajit Kundu
Kusuma School of Biological Sciences
Chemical composition
Small molecules- amino acids, nucleotides, sugars
Macromolecules- DNA, RNA, Protein
MOLECULAR BIOLOGY- study of the higher level of
molecular organization, interaction etc.
Covalent bonds
• Sharing of electrons
·
H
· ·S̈·
·P
·
¨
y
Readily forms covalent bonds with other atoms and rarely exists as isolated entities
x
s orbital
y
x
C forms four covalent-bonds
N forms four covalent bonds (one pair not involved in bonding –NH3)
In NH4+- N forms four covalent bonds.
Phosphorus can form up to 5 covalent bonds (H3PO4)
p orbital
y
x
d orbital
·
·P
·
Covalent bonds have characteristic geometry
Ethylene
Non-polar C-C, C-H
The making and breaking of bonds
Polar covalent bonds
Electronegativity. Fluorine- 4.0
Polar O-H (dipole moment)
Very stable
Energies required to break
or rearrange them are
much higher than the
thermal energy available at
room temperature.
Non-Covalent Bonds/interactions
Ionic interaction
H-Bonds
Van Der Waal’s interaction
Hydrophobic interaction
Non-Covalent Bonds
• Non-covalent bonds are critical in maintaining the
three-dimensional structure of large macromolecules
such as proteins and nucleic acids
• Although weak and transient at physiological
temperature, multiple NC-bonds often act together to
produce highly stable and specific associations
between different parts of a large molecule or between
different macromolecules
• The energy released in the formation of Non-Covalent
bond is only 1-5 KCal, much less than bond energies of
single C-C bonds (83 Kcal/mol)
• Because the average kinetic energy of molecules at RT
is ~ 0.6 Kcal/mol, many molecules have enough energy
to break the Non-Covalent bonds.
• These bonds are therefore referred to as interactions
Ionic Interactions
In some compounds, the bonded atoms are so different in
electronegativity that the bonding electrons are never shared:
NaCl
Ionic bonds (or interactions) results from the attraction of a
positively charged ion — a cation — for a negatively charged ion
— an anion.
Unlike covalent or hydrogen bonds, ionic bonds do not have fixed
or specific geometric orientations because the electrostatic field
around an ion —is uniform in all directions.
Crystals of salts such as Na+Cl− do have very regular structures
because that is the energetically most favorable way of packing
together positive and negative ions. The force that stabilizes
ionic crystals is called the lattice energy.
In aqueous solutions, simple ions
of biological significance, such as
Na+, K+, Ca2+, Mg2+, and Cl−, do
not exist as free, isolated entities.
Instead, each is surrounded by a
stable, tightly held shell of water
molecules
Characteristics
Most ionic compounds are quite soluble in water because a large
amount of energy is released when ions tightly bind water
molecules.
This is known as the energy of hydration.
Oppositely charged ions are shielded from one another by the
water and tend not to recombine.
Salts like Na+Cl− dissolve in water because the energy of hydration
is greater than the lattice energy that stabilizes the crystal
structure.
In contrast, certain salts, such as Ca3(PO4)2, are virtually insoluble
in water; the large charges on the Ca2+ and PO43− ions generate a
formidable lattice energy that is greater than the energy of
hydration
https://slideplayer.com/slide/8917512/
H- Bonds
Polar molecules, such as water, have a weak, partial negative charge at one
region of the molecule (the oxygen atom in water) and a partial positive
charge elsewhere (the hydrogen atoms in water).
Normally, a hydrogen atom forms a covalent
bond with only one other atom.
A hydrogen atom covalently bonded to a donor
atom, D, may form an additional weak
association, the hydrogen bond, with an
acceptor atom, A:
D-- H ++ :A -
D-- H +………:A -
In order for a hydrogen bond to form, the donor atom must
be electronegative, so that the covalent D—H bond is
polar. The acceptor atom also must be electronegative
In biological systems, both donors and
acceptors are usually nitrogen or oxygen
atoms, especially those atoms in amino
(—NH2) and hydroxyl (—OH) groups.
D-- H ++ :A -
D-- H +………:A -
Characteristics
1.
Most hydrogen bonds are 0.26 – 0.31 nm long, about twice the length of
covalent bonds between the same atoms.
2.
The hydrogen atom is closer to the donor atom, D, to which it remains
covalently bonded, than it is to the acceptor.
3.
The length of the covalent D—H bond is a bit longer than it would be if
there were no hydrogen bond, because the acceptor “pulls” the
hydrogen away from the donor.
4.
The strength of a hydrogen bond in water (≈5 kcal/mol) is much weaker
than a covalent O—H bond (≈110 kcal/mol).
5.
An important feature of all hydrogen bonds is directionality
The strengths of the hydrogen bonds in proteins and nucleic acids are only 1
to 2 kcal/mol, less than water
Van der Waals Interactions
• When any two atoms approach each other closely, they create a weak,
nonspecific attractive force that produces a van der Waals interaction
• These nonspecific interactions result from the momentary random
fluctuations in the distribution of the electrons of any atom, which give
rise to a transient unequal distribution of electrons, that is, a transient
electric dipole.
• If two noncovalently bonded atoms are close enough together, the
transient dipole in one atom will perturb the electron cloud of the other.
• This perturbation generates a transient dipole in the second atom, and the
two dipoles will attract each other weakly. Similarly, a polar covalent bond
in one molecule will attract an oppositely oriented dipole in another
• The strength of van der Waals interactions decreases rapidly with increasing distance; thus
these noncovalent bonds can form only when atoms are quite close to one another. However, if
atoms get too close together, they become repelled by the negative charges in their outer
electron shells. When the van der Waals attraction between two atoms exactly balances the
repulsion between their two electron clouds, the atoms are said to be in van der Waals contact
Properties
For a van der Waals interaction, the inter-nuclear distance is
approximately the sum of the corresponding radii for the two
participating atoms.
The energy of the van der Waals interaction is about 1
kcal/mol, only slightly higher than the average thermal energy
of molecules at 25 °C
Van der Waals interactions, as well as other noncovalent bonds,
mediate the binding of many enzymes with their specific
substrates (the substances on which an enzyme acts) and of
each type of antibody with its specific antigen
Hydrophobic interaction
• Nonpolar molecules do not contain ions, possess a dipole moment, or
become hydrated. Because such molecules are insoluble or almost insoluble
in water, they are said to be hydrophobic
• The covalent bonds between two carbon atoms and between carbon and
hydrogen atoms are the most common nonpolar bonds in biological systems.
• Hydrocarbons — molecules made up only of carbon and hydrogen — are
virtually insoluble in water
• The chemical structure of tristearin, or tristearoyl
glycerol, a component of natural fats. It contains
three molecules of the fatty acid stearic acid,
CH3(CH2)16COOH, esterified to one molecule of
glycerol, HOCH2CH(OH)CH2OH. One end of the
molecule is hydrophilic; the rest of the molecule is
highly hydrophobic
Multiple Noncovalent Bonds Can Confer Binding Specificity
Acknowledgements: Sincere thanks to
following sources of information
• http://genome.tugraz.at/MolecularBiology/WS11_Chapter02%20.pdf