Proteins Structure &

Functions
Lec Module 3

Far Eastern University

IAS – Dept. of Mathematics
Biochemistry Cluster
 Outline of the Topics:
• Amino Acids • Levels of Protein Structures
• Twenty (20) Proteinogenic • Primary
Amino Acids • Secondary
• Acid-Base Property of Amino • Tertiary
Acids • Quaternary

• Peptides • Functions
• Peptide Bond Formation • Types of Proteins Based on
• Peptide Drawing Function
• Peptide Naming • Structure-Function Relationship
in Proteins
Amino Acids
 Amino Acids
Amino acids are the basic unit of proteins. Each amino acid has the following
components:
• a carboxyl group (-COOH/ -COO-)
• an amino group (-NH2/ -NH3+)
• an α carbon – carbon adjacent to the carboxyl group
• an R group – side chain that gives each amino acid a unique property
 Amino Acids
There are twenty-two (22) proteinogenic amino acids, twenty (20) of which can be
found in the genetic code. Each amino acid has their own unique side chain.

These amino acids are classified based on the characteristics of their R group.
• Non-Polar amino acids
• Polar Neutral amino acids
• Acidic amino acids
• Basic amino acids
 Non-Polar Amino Acids
Glycine (Gly, G): Alanine (Ala, A): Valine (Val, V): Leucine (Leu, L): Isoleucine (Ile, I):
hydrogen methyl group isopropyl group isobutyl group sec-butyl group

Methionine (Met, M): Phenylalanine (Phe,F): Tryptophan (Trp, W): Proline (Pro, P):
thioether group benzyl group indole group cyclic

aromatic aromatic
Polar Neutral Amino Acids
Serine (Ser, S): Threonine (Thr, T): Tyrosine (Tyr, Y):
primary alcohol secondary alcohol phenol group

aromatic
Asparagine (Asn, N): Glutamine (Gln, Q): Cysteine (Cys, C):
β amide group γ amide group thiol group
Acidic Amino Acids
Aspartic Acid (Asp, D): Glutamic Acid (Glu, E):
β carboxyl group γ carboxyl group
Basic Amino Acids
Lysine (Lys, K): Arginine (Arg, R): Histidine (His, H):
ε amino group guanidino group imidazole group

aromatic
 Essential & Non-Essential Amino Acids
Essential amino acids are amino acids that are necessary for growth and normal
body functions but cannot be synthesized by the body. Hence, they must be
obtained through the diet.
 Chirality of Amino Acids
All protein-derived amino acids, EXCEPT glycine, have at least one (1) stereocenter
– the α carbon – and are therefore chiral.

The most common and naturally accruing configuration of amino acids is the L-
configuration.
 Acid-Base Property of Amino Acids
Amino acids may act as weak acids and bases within an aqueous environment.
Aside from the carboxyl and amino groups, the side chains may also be ionized at
varying pH.

Each functional group will gain or lose H atoms at various pH, and therefore have
different pKa.
 Acid-Base Property of Amino Acids
At pH lower than the pKa, the functional
group is protonated.

At pH higher than the pKa, the functional

group is deprotonated.
 Acid-Base Property of Amino Acids
At a certain pH, the net charge of an amino acid will become zero (0). At this point,
the amino acid is said to be a zwitterion, or is in its zwitterionic form.

The pH at which an amino acid becomes a zwitterion is its isoelectric pH (pI).

 Acid-Base Property of Amino Acids
Which ionization state of arginine is its zwitterionic form?
Peptides
 Peptide Bond Formation
Amino acids are linked to one another through amide bonds that are called peptide
bonds. These bonds are formed between the α-carboxyl group of the first amino
acid and the α-amino group of the next amino acid in the chain.
 Peptide Bond Formation
Amino acids bonded together by a peptide bond are generally referred to as amino
acid residues.
 Peptide Chains
Short chains of amino acids (up to 50 residues) are referred to as peptides, while
longer chains (>50 residues) are called polypeptides.
 Peptide Drawing and Naming
By convention, peptides are written from left to right, starting from the α-amino
group (the N-terminal) to the α-carboxyl group (the C terminal).

Peptides can be written based on the names of their amino acid residues, their
three letter code, or their one letter code.

Name: alanyltyrosinylaspartylglycine

3-letter Code: NH3+-Ala-Tyr-Asp-Gly-COO-

1-letter Code: NH3+-AYDG-COO-

 Peptide Naming
What are the amino acid residues present in the pentapeptide below?
 Peptides vs Proteins
Peptides are short chains of amino acids linked together by peptide bonds that can
be composed of approximately up to 50 residues.

Polypeptides are longer chains of amino acids, greater than 50 residues.

Proteins are biomolecules composed of one or more polypeptide chains that have
more complex, three-dimensional structures. Other molecules may also be present
in their structure in order to function.
Ex: Heme group – Hemoglobin
Sugar chains – Antibodies
Levels of Protein Structure
 Levels of Protein Structure
Protein structures are organized based on their levels of complexity.
• Primary – the amino acid sequence
• Secondary – folding in specific areas of the polypeptide
• Tertiary – 3D folding of the entire polypeptide
• Quaternary – arrangement of polypeptide chains
 Primary Structure
Primary (1°) Structure - the amino acid sequence of a polypeptide chain held
together by peptide bonds and disulfide bonds. A sequence of n number of amino
acids can produce 20n number of proteins.
 Primary Structure
Changing the primary structure of a protein can have significant effects on a
protein's functions and higher-order structures. This is especially observed when
the change involves amino acids of different properties.

antidiuretic hormone uterine contraction & milk secretion hormone

Amino Acid #2: Arginine Amino Acid #2: Leucine
(basic) (nonpolar, aliphatic)
Amino Acid #7: Phenylalanine Amino Acid #7: Isoleucine
(nonpolar, aromatic) (nonpolar, aliphatic)
 Primary Structure
Changing the primary structure of a protein can have significant effects on a
protein's functions and higher-order structures. This is especially observed when
the change involves amino acids of different properties.
 Secondary Structure
Secondary (2°) Structure - the 3D arrangements in localized regions of the
polypeptide chain. These structures are stabilized by hydrogen bonds between the
H atom of the amide group and the O atom of carbonyl group.
 Secondary Structure
There are two common types of secondary structures:
• α-helix
• β-pleated sheets
 Secondary Structure
α-Helix
• Spiral structure stabilized by
intramolecular H-bonds

• C=O of each peptide bond is

hydrogen bonded to the N-H
of the fourth amino acid
away

• All side chains point outward

 Secondary Structure
α-Helix
• Turn – complete rotation
• Pitch – advance within
one complete turn
• Rise – advance per
amino acid

• Turn = 3.6 amino acids

• Pitch = 0.54nm
• Rise = 0.15nm
 Secondary Structure
α-Helix
• Helices can be destabilized by certain factors:

• Presence of helix breakers – proline and glycine

• Electrostatic interactions – repulsion or attraction between charged
amino acid residues
• Steric strain – bulkiness of adjacent R-groups
 Secondary Structure
α-Helix

α-Keratin – ‘coiled coil’ structure; individual chains of

keratin are in α-helix
 Secondary Structure
α-Helix

Collagen – triple helix structure; individual chains of collagen are in

α-helix
 Secondary Structure
β-Pleated Sheets
• Zigzag structure stabilized by
interchain or intrachain H-bonds of
adjacent polypeptide chains

• Formed when 2 or more polypeptides

line side-by-side

• All side chains extend above or below

the sheet in an alternating sequence
 Secondary Structure
β-Pleated Sheets
• Two types of β-pleated sheets:

Anti-Parallel β-pleated sheets – peptide chains run in opposite directions

Parallel β-pleated sheets – peptide chains run in the same direction
 Secondary Structure
β-Pleated Sheets

Silk Fibroin – has both α-helices and β-pleated sheets

 Tertiary Structure
Tertiary (3°) Structure - 3D conformation of the entire polypeptide. These
structures are stabilized by numerous interactions between amino acid side
chains.

• Covalent Bonds
• H-Bonds
• Disulfide Bridges
• Salt Bridges (acid-base interaction)
• Hydrophobic Interactions
• Metal Ion Coordination
Tertiary Structure
Tertiary Structure

Myoglobin– monomeric protein with a heme group

 Quaternary Structure
Quaternary (4°) Structure - 3D conformation of multiple polypeptide chains. Not all
proteins have quaternary structures.

Some proteins are composed of two or more polypeptide chains called subunits.
The quaternary structure refers to the arrangement of these subunits.

The quaternary structure is stabilized by numerous interactions, similar to the

tertiary structure.
Quaternary Structure

Hemoglobin– a tetrameric protein with 2 α-subunits and 2 β-subunits

 Protein Classification
Proteins can be classified based on their structural shape or their composition.

Based on Shape:
• Fibrous
• Globular

Based on Composition:
• Simple
• Conjugated
 Protein Classification: By Shape
Fibrous Proteins
• Contain 3° structures organized
approximately parallel along a single
axis

• Consists of long fibers or large sheets

• Tend to be mechanically strong α-Keratin

• Insoluble to water

• Play structural roles

Collagen
 Protein Classification: By Shape
Globular Proteins
• Folded to a spherical shape

• Most polar side chains are on the

outside while nonpolar side chains
are buried inside the structure Hemoglobin Albumin

• Soluble in water

• Nearly all have substantial sections of

α-helices and β-sheets

• Varied metabolic functions (catalysis, Myoglobin Lactase

transport, etc.)
 Protein Classification: By Composition
Simple Proteins
• Only composed of amino acids

Albumin – a simple protein

Conjugated Proteins
• Contains non-protein components
called prosthetic groups
• Prosthetic groups may be lipids,
carbohydrates or metal ions

Hemoglobin – a conjugated protein

with heme prosthetic group
 Protein Denaturation
A protein in its natural, functional, three-dimensional conformation is said to be in
its native state.

Denaturation refers to a change in protein native conformation and leads to

disruption of protein function. May or may not be permanent.
 Protein Denaturation
Denaturing agents – physical or chemical agents that unfold, alter or destabilize
the native conformation of proteins

Physical Agents Chemical Agents

• High temperature • Acids and bases (change in pH)
• Vigorous shaking or agitation • Salts (change in ionic strength)
• Hydrostatic pressure • Organic solvents, e.g. urea,
• UV radiation alcohol
• Reducing agents, e.g. performic
acid, mercaptoethanol
• Detergents
• Heavy metals, e.g. Hg2+, Pb2+, Ag+
 Protein Hydrolysis
Protein hydrolysis refers to the loss of the primary structure. This involves the
breakage of the peptide bonds, producing free amino acids or smaller peptide
chains.

Hydrolysis may be partial or complete, and can be caused by acids, bases or

enzymes.
Functions of Proteins
 Protein Functions
Proteins serve many functions, including the following:
• Structure – for support, e.g. collagen, elastin

• Catalysis – enzymes

• Storage – for amino acid storage, e.g. casein, ovalbumin

• Transport – for transport of other substances, e.g. hemoglobin

• Regulation – for regulating bodily activities, e.g. insulin, glucagon

• Receptor – for response to external stimuli, e.g. neuron receptors

• Movement – e.g. myosin, actin

• Protection – e.g. antibodies, fibrinogen

Protein Functions
 Structure-Function Relationship of Proteins
Protein function is highly depended on its structure and amino acid composition.
Changes to the amino acid sequence can negatively impact protein function.

Examples
Proteins for catalysis must have amino
acids that can interact and bind with their
target molecule for the reaction to take
place.
 Structure-Function Relationship of Proteins
Protein function is highly depended on its structure and amino acid composition.
Changes to the amino acid sequence can negatively impact protein function.

Examples
Proteins meant for transport from one compartment of the cell to another can have its
polypeptide chain form a ‘channel’ where molecules can pass through.
 Structure-Function Relationship of Proteins
Protein function is highly depended on its structure and amino acid composition.
Changes to the amino acid sequence can negatively impact protein function.

Examples
Receptor proteins embedded in the cell membrane, e.g. insulin
receptors.

The cell membrane is largely nonpolar. In order for proteins to remain

embedded, they must have nonpolar amino acids in regions that interact with
the cell membrane.

Regions that interact with the aqueous interior and exterior of the cell should
mostly be polar amino acids.
ANSWER!

LECTURE WORKSHEET 3 ON CANVAS!

END
Thank you for listening!