Opening Prayer

REVIEW
QUESTIONS
Question

Which is the
main energy
source of our
body?
Answer

Carbohydrates
Question

What are the

elements present
in carbohydrates?
Answer

Carbon,
Hydrogen and
Oxygen
Question

Which is the best

test for the
presence of
carbohydrates?
Answer

Benedict’s
Test
Question

What is the
general formula
for
carbohydrates?
Answer

(CH2O)n
 What are the 3
examples of
monosaccharides?
Answer

Glucose,
galactose and
fructose
Question

What is the
formula of a
disaccharide?
Answer

C12H22O11
Question

What sugar has

5 carbons in the
structure?
Answer

Ribose
 Chapter Four
The Three-Dimensional
Structure of Proteins

Paul D. Adams • University of Arkansas

cengage.com/chemistry/campbell
1. To understand better the protein structure and its
function.
2. To determine the differences between primary,
secondary, tertiary and quaternary structures of
protein
3. To comprehend the protein folding dynamics.
4. To realize the essence of the proteins’ correct
folding and the consequences if it will not fold
correctly.
Protein Structure
• Many conformations are possible for proteins:
• Due to flexibility of amino acids linked by peptide
bonds
• At least one major conformations has biological
activity, and hence is considered the protein’s native
conformation
Scientists have estimated the number of cells in the
average human body, which is around 30 trillion.
 There are about
200 different types of cells in the
body:
1. red blood cells (erythrocytes)
2. skin cells
3. neurons (nerve cells)
4. fat cells
 PRIMARY STRUCTURE

1°structure: the sequence of amino acids in a

polypeptide chain, read from the N-terminal end to the
C-terminal end
Changes in just one amino acid in
sequence can alter biological
function, e.g. hemoglobin
associated with sickle-cell anemia
 SECONDARY STRUCTURE

Secondary structure refers to regular,

repeated patterns of folding of the protein
backbone.

2°structure: the ordered 3-dimensional

arrangements (conformations) in localized
regions of a polypeptide chain; refers only
to interactions of the peptide backbone
e. g., -helix and -pleated sheet
2˚ Structure

• 2˚ of proteins is hydrogen-
bonded arrangement of
backbone of the protein
• Two bonds have free
rotation:
1) Bond between -
carbon and amino
nitrogen in residue
2) Bond between the -
carbon and carboxyl
carbon of residue
-Pleated Sheet (Cont’d)

Hydrogen
bonding in
b-pleated
sheets.
Alpha helix, the polypeptide backbone
coils around an imaginary helix axis in
clockwise direction or right-handed
.
Closer look of the 𝛂 - HELIX
Beta sheet secondary structure,
the polypeptide backbone is
nearly fully extended.
-Pleated Sheet (Cont’d)

The three-dimensional
form of the
antiparallel b-pleated
sheet arrangement. The
chains do not fold back
on each other but are in
a fully extended
conformation.
-Helices and -Sheets
-Helices and -Sheets
-Helices and -Sheets
 -Helices and -Sheets

A linked series of 𝛃 – meanders

arrangement
-Helices and -Sheets
-Helices and -Sheets
𝛃 - Barrel
Proline Cis−Trans Isomerization and
Protein Folding
The Triple Helix of Collagen

A triple helix. Poly

(Gly!Pro!Pro)
is a collagen-like
right-handed triple
helix composed
of three left-handed
helical chains.
Tertiary (3°) structure:
the arrangement in
space of all atoms in a
polypeptide chain
it is not always
possible to draw a
clear distinction
between 2°and
3°structure
Forces Involved in 3˚ Structure

• Noncovalent interactions, including

• hydrogen bonding between polar side chains, e.g.,
Ser and Thr
• hydrophobic interaction between nonpolar side
chains, e.g., Val and Ile
• electrostatic attraction between side chains of
opposite charge, e.g., Lys and Glu
• electrostatic repulsion between side chains of like
charge, e.g., Lys and Arg, Glu and Asp
• Covalent interactions: Disulfide (-S-S-)
bonds between side chains of cysteines
Large Numbers of Data Points Needed to
Determine 3˚ of a Protein

the structure of myoglobin as

determined by X-ray crystallography.
The Structure of Myoglobin and the Heme
Group
The peptide backbone and
the heme group are
shown overlain on the
space-filling model. The
helical segments are
designated by the letters
A through H. The terms
NH3 and COO2 indicate the
N-terminal and C-terminal
ends, respectively.
4˚ structure: arrangement of monomer subunits with respect to
each other
Quaternary (4°) structure: the association of polypeptide
chains into aggregations
Proteins are divided into two large classes based on their
three-dimensional structure
fibrous proteins
globular proteins
Fibrous Proteins
• Fibrous proteins: contain polypeptide chains
organized approximately parallel along a single axis.
They
• consist of long fibers or large sheets
• tend to be mechanically strong
• are insoluble in water and dilute salt solutions
• play important structural roles in nature
• Examples are
• keratin of hair and wool
• collagen of connective tissue of animals including
cartilage, bones, teeth, skin, and blood vessels
 FIBROUS PROTEIN

Filament (four
right-hand
twisted
protofilaments
Globular Proteins
• Globular proteins: proteins which are folded
to a more or less spherical shape
• they tend to be soluble in water and salt solutions
• most of their polar side chains are on the outside
and interact with the aqueous environment by
hydrogen bonding and ion-dipole interactions
• most of their nonpolar side chains are buried inside
• nearly all have substantial sections of -helix and
-sheet
 GLOBULAR PROTEIN

Computer generated model of a globular

protein. Alpha-helices are shown in blue, beta-
sheets are green, and random coil is gold
Quaternary Structure of Proteins
• Quaternary (4°) structure: the association of
polypepetide monomers into multisubunit proteins.
Some common multi-subunits include:
• dimers
• trimers
• tetramers

• Noncovalent interactions
• electrostatics, hydrogen bonds, hydrophobic
Structure of Hemoglobin

The structure of hemoglobin. Hemoglobin (α2β2) is a

tetramer consisting of four polypeptide chains
(two α-chains and two β-chains).
The Structures of Oxy- and Deoxyhemoglobin

Note the motions of subunits with respect to one another.

There is much less room at the center of oxyhemoglobin.
Hydrophobic Interactions: A Case Study in
Thermodynamics
• Hydrophobic interactions are major factors in protein
folding
• Folding occurs so that nonpolar hydrophobic side
chains tend to be on inside away from water, and
polar side chains on outside accessible to aqueous
environment
• Hydrophobic interactions are spontaneous
• An introduction to this concept has been described in
the description of the formation of liposomes
Schematic Diagram of a Liposome
Hydrophobic and Hydrophilic Interactions in
Proteins

The three-dimensional structure of

the protein cytochrome
The Importance of Correct Folding
• Proteins that do not fold correctly may interact with other
proteins in an undesired manner and aggregates may result.

The problem of protein aggregation.

(a) Partly folded polypeptide chains, released from ribosomes (the protein-
synthesizing machines), normally form correctly folded, functional proteins.
(b) However, partly folded proteins may sometimes associate with similar chains
to form aggregates.
Both soluble and insoluble aggregates can be toxic
to cells.
Protein Folding Chaperones
• In the protein-dense environment of a cell, proteins
may begin to fold incorrectly or may associate with
other proteins before folding is completed
• Special proteins called chaperones aid in the correct
and timely folding of many proteins
• Chaperones exist in organisms from prokaryotes to
humans

It is important for the chaperone to always perform its

responsibility to make sure that protein will have a
correct folding in order to perform its function.
Remember that if the folding of the protein is not
correct, it will not be functional.
 Words to Ponder
What most people don’t
realize is that food is not just
calories; it’s information.
It actually contains
messages that connect to
every cell in the body.”
Dr. Mark Hyman