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Proteins – Structure & Properties
MBC 224- Level-3
By Dr.Charles Stephen D
Origin of
Specificity
Function
is critically
dependent
on
structure
1ruv.pdb
Fold of a
Protein
Refers to the spatial arrangement of its secondary structural elements (ahelices and b-strands)
1l45.pd
b
a/b-barrel
4bcl.pd
b
b-barrel
1mbl.pd
b
a/b-sandwich
Introduction
• Proteins are the most abundant and functionally
diverse molecules in living systems
• All process of life depends on these molecules
• Enzymes (proteins) and peptide hormones
regulate metabolism in the body
• Contractile proteins in muscle permit movements
• In the blood, hemoglobin, immunoglobulin and
albumin do major function
• Proteins are linear polymers of amino acids
Proteins: What are they?
FUNCTIONS
• Structural
– Support - connective
tissue
– Keratin – hair, finger
nails
• Transport
– Hemoglobin
Proteins: What are they?
• Some Hormones
– Coordinate body activity (insulin, growth horm.)
• Muscles (actin, myosin)
What are they made of?
• Proteins are polymers
– Poly = many
– Polymers = LARGE molecules made of
smaller, repeating units, called Monomers
• These monomers are made up of C, H, O, N, and
some S (carbon, hydrogen, oxygen, nitrogen, sulfur)
• Monomers are called Amino Acids…
Structure of Amino acids
• There are > 300 amino acids exist in nature
• But only 20 amino acids are found in all
proteins
• Each amino acid has a carboxyl group, an
amino group and distinctive side chain called
R group bonded to the α carbon atom.
L-Form Amino Acid Structure
Carboxylic group
Amino group
+
H3 N
R group
COO
a
-
H
H = Glycine
CH3 = Alanine
Juang RH (2004) BCbasics
Classification of Amino acids (AA)
• Since the amino and carboxyl groups are
common for all 20 amino acids, the R group
is different for each amino acid.
• Hence, based on the R group the AA are
classified into four groups, namely (1)
Nonpolar side chain, (2) Uncharged polar
side chain (3) Acidic side chain and (4) basic
side chain amino acids.
Non polar side chain AA
• There are 9 AA in this group - namely,
glycine, alanine, valine, leucine, isoleucine,
methionine, proline, phenyalanine &
tryptophan.
• These groups are hydrophobic (water
repellent) and lipophilic.
• Therefore, the parts of proteins made up of
these amino acids will be hydrophobic in
nature.
Nonpolar side chain - AA
Uncharged, polar AA
• Serine, Threonine,, Tyrosine, Aspargine,
Cysteine and Glutamine belong to this group.
• Serine, threonine and tyrosine have ‘OH’
group in the side chain
• Aspargine and glutamine have amide group
(CO-NH) and cysteine has a thiol (-SH) group
in the side chain which can be hydrophilic in
water
Uncharged polar side chain AA
Acidic & Basic side chain AA
• They have a negative charge on the R group
• Aspartic acid and glutamic acid are the two
AA
• The negative group is contributed by carboxyl
group – COO• Three AA have a positive charge on their R
group, they are histidine, lysine and arginine.
Acidic side chain AA
Basic side chain AA
Classification of Amino Acids by Polarity
NONPOLAR
POLAR
Acidic
Neutral
Basic
Asp
Asn Ser
Arg
Cys
Tyr
His
Gln
Thr
Lys
Glu
Gly
Ala Ile
Phe Trp
Val Leu Met Pro
Polar or non-polar, it is the bases of the amino acid properties.
Juang RH (2003) Biochemistry
AA with three letters- single letter
Properties of AA
• 1. Optical property: The α carbon of each amino
acid is attached to four different groups and is,
therefore, a chiral or optically active carbon atom.
Glycine is exception because its α carbon has two
H atoms, so it is optically inactive.
• The α carbon can exist in two forms which are
mirror image of each other, L form and D form. They
are called stereoisomer or enantiomers.
• All amino acids found in proteins are L configuration
However, D amino acids are found in antibiotics
and in bacterial cell walls.
Mirror Images of Amino Acid
a
Mirror
image
a
Same chemical properties
Stereo isomers
Juang RH (2004) BCbasics
Properties of AA contd…
• Amino acids in aqueous solution contain
weakly acidic carboxyl group and weakly
basic amino group.
• In addition, the acidic and basic amino acids
contain an ionizable group in the side chain
• So amino acids are ampholytes, ie, they can
act as an acid or a base.
• They (in proteins) can act as good buffers in
biological systems
Properties contd…
• Amino acids can form zwitter ions
• If the net charge of an amino acid is zero, that
form is called a dipolar form or isoelectric form or
zwitter ionic form.
Environment pH vs Protein Charge
Buffer pH
10
9
8
7
Isoelectric point,
pI
+
6
5
4
3
0
-
-
Net Charge of a Protein
Juang RH (2004) BCbasics
Structure of Proteins
• The 20 AA found in proteins are joined
together by peptide bonds
• The linear sequence of the linked AA
contains the information to form a protein
molecule with a unique three-dimensional
structure or shape.
• The structure of proteins are described in four
levels, namely primary, secondary, tertiary
and quaternary.
How are proteins constructed
• First the Amino
acids bond together.
• They are joined
together by what is
known as a peptide
bond.
Formation of a peptide bond via
condensation.
H
R
N
H
C
O
C
H
+
N
H
C
O
C
H
OH
Amino acid
R
H
Amino acid
OH
A peptide bond between two amino
acids.
H
N
H
R
C
H
O
C
H
N
H
C
R
O
C
OH
H20 [WATER]
A condensation reaction
Formation of Peptide Bonds by Dehydration
Amino acids are connected head to tail
NH2
1
COOH
2
NH2
COOH
Dehydration
Carbodiimide
-H2O
O
NH2
1
C N
2
COOH
H
Juang RH (2004) BCbasics
Protein construction
• When two amino acids join together
they form a dipeptide.
• When many amino acids are joined
together a long-chain polypeptide is
formed.
• Organisms join amino acids in
different linear sequences to form a
variety of polypeptides in to complex
molecules, the proteins.
Amino acid
Peptide bond
Primary protein structure
primary
structure
This is the linear sequence of amino acids
Primary Structure
• The linear sequence of amino acids in a
protein is called the primary structure.
• The sequence is determined by information
present in the DNA. Any defect in the genetic
code leads to abnormal proteins. Eg: sickle
cell anemia.
• The amino acids are joined covalently by
peptide bonds, which are amide linkage
between the α carboxyl group of one amino
acid, and α amino group of another by
removing one molecule of water.
Formation of peptide bond
Primary structure contd…
• Peptide bonds are not broken by protein
denaturation, only with strong acid or base these
bonds are broken. The proteases present in the
digestive tract cleaves the bond.
• The free amino end of a peptide chain is written to
the left and called N-terminal end.
• The free carboxyl end is written to the right and
called C-terminal end.
• The AA in a peptide chain is called a ‘residue’ or
‘moiety.’
• The peptide consisting two AA is a dipeptide, three
AA, a tripeptide, four AA a tetra peptide and so on.
Peptides with few AA are called oligopeptides,10 -50
AA are called polypeptides & >50 AA are called
proteins.
Secondary protein structure
Polypeptides become twisted or coiled.
These shapes are known as the secondary
Structure.
There are two common secondary structures
The alpha-helix and the beta-pleated sheet.
Secondary protein structure
Alpha-helix
Amino acid
Hydrogen bonds hold shape
together
Secondary Protein structure
[The beta pleated sheet]
Amino acid
Secondary Structure
• When the polypeptide chain
assume a regular recurrent
rearrangement, then the
structure is termed as
‘secondary structure’
• α helix and β pleated sheet
are examples of secondary
structure
• Hydrogen bonds are the
main chemical force which
maintain secondary
structure
Tertiary protein structure
• This is when a polypeptide is folded
into a precise shape.
• The polypeptide is held in ‘bends’
and ‘tucks’ in a permanent shape by
a range of bonds including:
• Disulphide bridges [sulphur-sulphur
bonds]
• Hydrogen bonds
• Ionic bonds.
Tertiary protein structure
Quaternary protein structure
Tertiary & Quaternary Structures
• When the polypeptide chain
attains a shape with twisting,
folding, and super folding in
a three dimensional position,
then the structure is said to
be ‘ tertiary ‘.
• Disulfide bond,Hydrogen
bond, Hydrophobic
interactions are responsible
for this structure.
• When more than one
polypeptide chain, in a
protein, attain a three
dimensional shape, then it is
called ‘quaternary’ structure.
Two polypeptide chains are
‘dimeric’, three pp chains are
‘trimeric’ proteins etc.
Forces responsible for protein
structure
• 1.Hydrogen bond: Between the Hydrogen atom
and carbonyl oxygen or amide Nitrogen (strong
electro negative atoms)
• 2.Disulfide bond: is a covalent bond between the
sulfhydryl (-SH) group of two cysteine residues.
• 3.Hydrophobic interactions: AA with non polar R
groups tend to be located in the interior of the
structure.
• 4.Ionic interaction: Negatively charged group such
as COO- can interact with positively charged groups,
such as the amino group NH3+
Hydrogen,Ionic & Disulfide bonds
Protein Denaturation
• Protein denaturation results in the unfolding and
disorganization of the protein’s secondary and
tertiary structures
• The peptide bonds are NOT hydrolyzed, (not
broken)
• Denaturing agents include, heat, organic solvents,
mechanical mixing, strong acids, or bases,
detergents, ions of heavy metals such as lead or
mercury.
• Denatured protein becomes less soluble and gets
precipitated.
• Denaturation may be reversible.
Classification of Proteins
There are many ways to classify the proteins.
This classification is based on the functions of
proteins.
1. Catalytic proteins: enzymes
2. Structural proteins: collagen, elastin, keratin
3. Contractile proteins: myosin, actin,
4. Transport proteins: hemoglobin, myoglobin,
albumin, transferin
5. Regulatory proteins: insulin, growth hormone
6. Genetic proteins: histones
7. Protective proteins: immunoglobulin, interferon,
clotting factors.
Fibrous & Globular proteins
• Fibrous proteins are elongated proteins
(lengthy) and mostly form the structures like
the cell membrane , connective tissue etc
• Collagen and elastin are examples, which
are present in the skin, connective tissue and
blood vessel walls
• Globular proteins have specialized functions
• Enzymes, Hemoglobin and proteinhormones are some examples.