Amino Acids

Amino acids are molecules that combine to form proteins.

The elements present in every amino acid are carbon (C),

hydrogen (H), oxygen (O), and nitrogen (N); in addition sulfur (S).

As many as 300 amino acids occur in nature. Of these, only 20-

known as standard amino acids are repeatedly found in the
structure of proteins, isolated from different forms of life- animal,
plant and microbial.
 Amino Acids Share Many Features,
Differing Only at the R Substituent

FIGURE 3-2 General structure of

an amino acid. This structure is
common to all but one of the α-amino
acids. (Proline, a cyclic amino acid, is
the exception.) The R group, or side-
chain (red), attached to the α carbon
(blue) is different in each amino acid.
Amino Acids Have Three Common Functional
Groups Attached to the α Carbon
• The α carbon always has four substituents and is
tetrahedral.
• All (except proline) have:
– an acidic carboxyl group connected to the α carbon
– a basic amino group connected to the α carbon
– an α hydrogen connected to the α carbon
• The fourth substituent (R) is unique in glycine, the
simplest amino acid. The fourth substituent is also
hydrogen.
All Amino Acids Are Chiral (Except Glycine)
Proteins only contain L amino acids

FIGURE 3-3 Stereoisomerism in

α-amino acids.

CRN Rules

cLock
 Amino Acids: Classification

Common amino acids can be placed in five basic

groups depending on their R substituents:
• nonpolar, aliphatic (7)
• aromatic (3)
• polar, uncharged (5)
• positively charged (3)
• negatively charged (2)
These amino acid side chains absorb UV light at 270–280 nm
These amino acids side chains can form hydrogen bonds.
Cysteine can form disulfide bonds.
 Four Levels of Protein Structure

The term protein is generally used for a polypeptide

containing more than 50 amino acids.
The primary structure of a protein refers to the sequence of amino
acids in the polypeptide chain. The primary structure is held together
by peptide bonds that are made during the process of protein
biosynthesis.
 Amino Acids Polymerize to Form Peptides
• Peptides are small condensation products of amino
acids.
• They are “small” compared with proteins (Mw < 10 kDa).

FIGURE 3-13 Formation of a peptide bond by condensation. The α-amino group of one amino acid (with R2
group) acts as a nucleophile to displace the hydroxyl group of another amino acid (with R1 group), forming a
peptide bond (shaded in yellow). Amino groups are good nucleophiles, but the hydroxyl group is a poor leaving
group and is not readily displaced.
 Secondary Structure: α Helix
Secondary structure refers to short-range,
periodic folding elements that are common in
proteins. These include the α helix, the β
sheet, and turns.
❖ In the α-helix, the backbone adopts a
cylindrical spiral structure in which there
are 3.6 AAs per turn.
❖ The R-groups point out from the helix, and
mediate contacts to other structure
elements in the folded protein.
❖ The α helix is stabilized by H-bonds
between backbone carbonyl oxygen and
amide nitrogen atoms that are oriented
parallel to the helix axis.
 Secondary Structure: β Sheets
In β sheets, each β-strand adopts an
extended conformation.
β strands tend to occur in pairs or multiple
copies in β sheets that interact with one
another via H-bonds directed
perpendicular to the axis of each strand.
Carbonyl oxygens and amide nitrogens in
the strands form the H-bonds.
Strands can orient antiparallel or parallel to
one another in β sheets. R-groups of every
other amino acid point up or down relative
to the sheet.
Most β strands in proteins are 5 to 8 AAs
long.
 Tertiary Structure
The overall three-dimensional structure of a polypeptide is
called its tertiary structure. The tertiary structure is primarily
due to interactions between the R groups of the amino acids that
make up the protein.

R group interactions that contribute to tertiary structure include

hydrogen bonding, ionic bonding, dipole-dipole interactions, and
London dispersion forces – basically, the whole gamut of non-
covalent bonds. For example, R groups with like charges repel
one another, while those with opposite charges can form an ionic
bond.
Similarly, polar R groups can form
hydrogen bonds and other dipole-
dipole interactions. Also important to
tertiary structure are hydrophobic
interactions, in which amino acids
with nonpolar, hydrophobic R groups
cluster together on the inside of the
protein, leaving hydrophilic amino
acids on the outside to interact with
surrounding water molecules.

Finally, there’s one special type of

covalent bond that can contribute to
tertiary structure: the disulfide bond.
Covalent cross-linkages
stabilise these proteins by
connecting specific amino
acids within a polypeptide
or between polypeptide
chains in multisubunit
proteins. Typically such a
linkage will be a covalent
sulfur–sulfur bond which
forms between the –SH Figure: An example of how the formation
groups of two cysteine of a disulfide bond between cysteine side
residues that are in close chains stabilize existing structures in a
polypeptide. These bonds can form
proximity in the folded between two polypeptide strands or
protein. between residues in the same polypeptide.
 Quarternary Structure
Many proteins are made up of a single polypeptide
chain and have only three levels of structure.
However, some proteins are made up of multiple
polypeptide chains, also known as subunits. When
these subunits come together, they give the protein
its quaternary structure.

The quaternary structure of a protein is the

association of several protein chains or subunits into
a closely packed arrangement. Each of the subunits
has its own primary, secondary, and tertiary structure.
The subunits are held together by hydrogen bonds
and van der Waals forces between nonpolar side
chains.
 Denaturation & Renaturation
Denaturation is the process of modifying the conformation of the
protein structures without rupturing the native peptide linkages.
❖This inactivates the functionality of the protein molecules,
decreases its solubility, decreases/destroys its biological activity,
improves digestibility and alters the water binding ability of the
molecule.
❖Denaturation of proteins is achieved by disrupting the hydrogen
bonding in the peptide linkage by applying external stress.
❖It can be carried out by applying heat, treatment with alcohols,
heavy metals, or acids/bases.
Renaturation of a protein is the conversion of a denatured
protein back into its native 3D structure. Therefore, it involves
the reconstruction of a protein molecule after losing its original
structure.
Renaturation is the inverse process of denaturation. Renaturation
is sometimes reversible. However, renaturation is not common
and easy as denaturation.
 Zwitter Ion
A zwitter ion is a molecule with functional groups, of which at least one
has a positive and one has a negative electrical charge. The net charge of
the entire molecule is zero.
Amino acids are the best-known
examples of zwitter ions. They
contain an amine group (basic)
and a carboxylic group (acidic).
The -NH2 group is the stronger
base, and so it picks up H+ from
the -COOH group to leave a
zwitter ion (i.e. the amine group Alanine act as
de-protonates the carboxylic zwitterion at pH 7.3.
acid).
Classification of Protein based on Biological Functions

1. Catalytic protein:
They catalyze biochemical reaction in cells. Eg. Enzymes and co-
enzymes
2. Structural protein:
They make various structural component of living beings.
Eg. Collagen make bone, Elastin make ligaments and keratin make
hair and nails
3. Nutrient protein:
They have nutritional value and provide nutrition when consumed.
Eg. Casein in milk
4. Regulatory protein:
They regulate metabolic and cellular activities in cell and tissue.
Eg. Hormones
5. Defense protein:
They provide defensive mechanism against pathogens.
Eg. Antibodies, complement proteins
6. Transport protein:
They transport nutrients and other molecules from one organ to
other. Eg. Haemoglobin
7. Storage protein:
They stores various molecules and ions in cells.
Eg. Ferritin store Iron
8. Contractile or mobile protein:
They help in movement and locomotion of various body parts. Eg.
Actin, myosin, tubulin etc
9. Toxic protein:
They are toxic and can damage tissues.
Eg. Snake venom, bacterial exotoxins etc
Classification of Protein based on Chemical Composition
 Simple Proteins
1. Fibrous Protein

Collagen
2. Globular Protein

Albumin
Fibrous Vs Globular Protein
 Conjugated Proteins
❑ Nucleoprotein, a conjugated protein consisting of a protein linked
to a nucleic acid, either DNA (deoxyribonucleic acid) or RNA
(ribonucleic acid).
❑ Glycoprotein is a compound containing carbohydrate covalently
linked to protein. A mucoprotein is a glycoprotein composed
primarily of mucopolysaccharides.
❑ Lipoprotein, any member of a group of substances containing both
lipid (fat) and protein.
❑ Phosphoprotein is a protein that is post-translationally modified
by the attachment of either a single phosphate group, or a complex
molecule such as 5'-phospho-DNA, through a phosphate group.
❑ Chromoprotein is a conjugated protein that contains a
pigmented prosthetic group. A common example is
haemoglobin, which contains a heme cofactor, which is the
iron-containing molecule that makes oxygenated blood appear
red.
❑ Metalloproteins are a large group of enzyme proteins which
contain metallic elements such as iron, copper, cobalt,
manganese, and others.

A prosthetic group is the non-amino acid component that is part of the

structure of the heteroproteins or conjugated proteins.
 Derived protein

These protein are the derivatives of either simple or complex

protein resulting from the action of heat, enzymes and chemicals.
Some artificially produced protein are included in this group.
Example: Albumose (derived from albumins)
 Non-Standard Amino Acids
Besides the 20 amino acids present in the protein
structure, there are several other amino acids that are biologically
important.
✔Collagen-the most abundant protein in mammals-contains 4-
hydroxyproline and 5-hydroxylysine.
✔Histones-the proteins found in association with DNA, contain many
methylated, phosphorylated or acetylated amino acids.
✔γ-Carboxyglutamic acid is found in certain plasma proteins involved
in blood clotting.
✔D-Penicillamine (D-dimethylglycine), a metabolite of penicillin, is
employed in the chelation therapy of Wilson’s disease. This is possible
since D-penicillamine can effectively chelate copper.