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ERT106 BIOCHEMISTRY
PROTEIN
Pn Syazni Zainul Kamal
Protein structure
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Protein (polypeptides) are organic compound
made of amino acids arranged in a linear form
and folded into specific conformation
Protein - essential part of organisms
- participate virtually in every process
within cells
Protein structure
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When cell synthesizes a polypeptides, the chain
folded spontaneously
This folding is reinforced by variety of bonds
between the chain
In a complex structure of protein, several levels
of the structural organization of proteins :
a) primary structure
c) tertiary structure
b) secondary structure
d) quaternary structure
a) Primary structure
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Primary structure of protein is its unique
sequence of amino acids forming its
polypeptide chain
Every polypeptides has a specific amino acid
sequence
the primary structure of a protein is starting
from the amino-terminal (N) end to the
carboxyl-terminal (C) end
Primary structure of enzyme lysozyme
b) Secondary structure
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Most proteins have segments of their polypeptide
chain repeatedly coiled of folded in patterns.
These coiled & folded referred as secondary
structure.
2 types of secondary structure :
- α-helix
stabilized by hydrogen bond
- β-pleated sheet between carbonyl & amino groups
in the polypeptide’s backbone
α-helix
 Rigid, rodlike structure when a polypeptides
chain twists into a right-handed helical
conformation
 Hydrogen bond form between amino group of
each amino acid and the carbonyl group of the
amino acid four residue away (H bond form
between 4 amino acid)
 R group extend outward from the helix
β-pleated sheet
 Form when two or more polypeptide chain
segments line up side by side
 Each individual segment = β-strand
 Each β-strand is fully extended
 β-pleated sheet stabilized by hydrogen bonds
form between the polypeptide backbone N-H and
carbonyl groups of adjacent chains
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Two β-pleated sheet :
- parallel - polypeptide chain arranged in same
direction
- antiparallel - polypeptide chain arranged in
opposite direction
- more stable
Usually mixed parellal-antiparallel β-pleated
sheet observed in proteins
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combination of α-helix and β-pleated sheet
secondary structure = supersecondary structure
Supersecondary structure :
a) βαβ unit two parallel β-pleated sheets
connected by α-helix
fragment
b) β-meander two antiparallel β-sheets are
connected by polar amino acids and glycines
to effect an abrupt change in direction of the
polypeptide chain (reverse or β-turns)
b meander
c) αα-units two α-helices separated by loop
or nonhelical segment
d) β-barrel form when various β-sheet
configurations fold back on themselves
e) Greek key antiparallel β-sheet doubles back
on itself in a pattern that resemble a common
greek pottery design
c) Tertiary structure
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Three-dimensional structure of a single protein
molecules
The α-helices and β-pleated sheets are folded
into compact globule.
Protein folding occurs as consequence of
interactions between the side chains in their
primary structure
Interactions that stabilize tertiary
structure
1) Hydrophobic interactions
 As polypeptide folds, amino acids with
hydrophobic (nonpolar) side chain are brought
close to each other, out of contact with water.
2) Electrostatic interactions
 Interaction occurs between ionic groups of
opposite charge (referred as salt bridge)
3) Hydrogen bonds
 Large number of hydrogen bond form within a
protein’s interior and on its surface
 Examples of amino acid side chains that may
hydrogen bond to each other:
 Two alcohols: ser, thr, and tyr.
Alcohol and an acid: asp and tyr
Two acids: asp and glu
Alcohol and amine: ser and lys
Alcohol and amide: ser and asn
4) Covalent bond
 Created by chemical reactions that alter a
polypeptide's structure during or after its
synthesis
 eg. Disulphide bond (strong linkage)
 Protect protein structure from adverse changes
in pH or salt concentrations
d) Quaternary structure
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Proteins consist of two or more polypeptide chains
aggregated into one functional macromolecules
Many proteins, esp those with high molecular weight
are composed of several polypeptide chains.
In proteins that consist of more than 1 polypeptide
chain, each polypeptide is called subunit
Polypeptide subunits assemble and held together by
noncovalent interaction eg H bonding, hydrophobic
effect, electrostatic interaction
Loss of protein structure
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Protein structure is sensitive to environment
factors
Many physical & chemical agents can disrupt
protein’s conformation
The process of structure disruption =
denaturation
Denaturing conditions :
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Strong acid or base – changes in pH result in
protonation of some protein side group, which
alter/disrupt hydrogen bonding & salt bridge
Organic solvents – water-soluble organic
solvents eg. Ethanol interfere with
hydrophobic interaction
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Detergents – these amphiphatic molecules
disrupt hydrophobic interaction causing
proteins to unfold into extended polypeptide
chains
(amphiphatic = contain nonpolar and polar
components)
Reducing agents – eg. Urea, βmercaptoethanol, will convert disulfide bridge
(S-S) to sulfhydryl group (SH)
urea disrupt H bond & hydrophobic interaction
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Heavy metal ions – mercury (Hg+) and lead
(Pb2+) disrupt salt bridge by forming ionic bond
with negatively charge group.
Temperature change – as temp increase, the rate
of molecular vibration increase. So weak H
bond will be disrupt and protein will unfold.
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Mechanical stress – stirring & grinding actions
disrupt the delicate balance of forces that
maintain protein strcuture.
eg. Foam formed when egg white is beaten
vigorously contains denatured protein
Fibrous proteins
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Fibrous protein exist as a long stranded
molecules
Contain high proportions of secondary
structures ; α-helices and β-pleated sheets
Most are structural protein
eg. α-keratin, collagen, silk fibroin
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α-keratin
Found in hair, wool, skin, horns, fingernails is
an α-helical polypeptides
Each polypeptide has three domain :
- an amino terminal ‘head’
- a central rodlike α-helical domain
- a carboxyl terminal ‘tail’
Two keratin polypeptides associate to form =
coiled coil dimer
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Two keratin polypeptides associate to form =
coiled coil dimer
Two antiparallel rows of these dimer form a
supercoiled structure called a protofilament
(disulfide bond aid the formation of
protofilament)
Hundreds of filaments, each containing 4
protofilaments form macrofibril
Each hair cells (fiber) contain several
macrofibrils
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Collagen
The most abundant protein in vertebrates
Synthesized by
- connective tissue cells
mostly found in fibrous tissues such as :
tendon, ligament and skin, in cornea, cartilage,
bone, blood vessels, the gut
Extremely strong
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Collagen is composed of three
polypeptide helices that are twisted
around each other to form a triple helix
(stabilized by hydrogen bonding)
The amino acid composition of collagen
is distinctive
- high content of glycine, proline and
lysine
- very little amount of cysteine (unlike αkeratin)
Silk fibroin
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Silk protein
- form spider webs, cocoon and nests
- consist of the fibrous protein fibroin
Considered to be β-keratin
- polypeptide chains arranged in antiparallel βpleated sheet comformation
Its primary structure mainly consists of the
amino acid sequence (Gly-Ser-Gly-Ala-GlyAla)n
Globular protein
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Globular protein have a spherical shape,
compact and water-soluble
In their function, usually require them to bind
precisely to other molecules
Most enzyme are globular
Myoglobin & hemoglobin are typical example
of globular protein
Both are hemoprotein and each is involved in
oxygen metabolism
Unlike fibrous proteins which only play a structural
function, globular proteins can act as:
1) Enzymes, by catalyzing organic reactions taking
place in the organism in mild conditions and with a
great specificity.
2) Messengers, by transmitting messages to regulate
biological processes. This function is done by
hormones, i.e. insulin etc.
3) Transporters of other molecules through membranes
4) Stocks of amino acids.
5) Regulatory roles are also performed by globular
proteins rather than fibrous proteins.
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a) Myoglobin
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Myoglobin is an iron- and oxygen-transport
protein found in the muscle tissue of vertebrates
in general and in almost all mammals.
composed of a single polypeptide chain of 153
amino acid residues and has the ability to store
oxygen by binding it to an iron atom (heme)
It is found abundantly in the tissues of diving
mammals, e.g., the whale, the seal, and the
dolphin.
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High concentrations of myoglobin in these
animals, allows them to store sufficient oxygen
to remain underwater for long periods.
A myoglobin polypeptide is comprised of 8
separate right handed α-helices, that are
connected by short non helical regions.
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Each myoglobin molecule contains one heme
prosthetic group
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Each heme consist of porphyrin ring with Fe2+
in the center
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Free heme [Fe2+] has a high affinity for O2 and
is irreversibly oxidized to form hematin [Fe3+]
b) Hemoglobin
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Hemoglobin is a roughly spherical molecule
found in red blood cells
Function = transport oxygen from lung to
every tissues in the body
Composed - two α-chain
- two β-chain
The protein contain four subunits, designated α
and β. Each subunit contain a heme group that
bind with oxygen