General Structure of

Proteins
Ma. Paulina Isabel P. Santos, PharmD, RPh
 Objectives
At the end of the discussion, the students must be
able to:

• Demonstrate knowledge and understanding of the

general structure of proteins

• Identify the importance of these structures and

distinguish key factors in their formation.

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 Importance
Proteins serve different biological functions, serving as:

• Catalytic proteins such as amylase, lipase

• Storage proteins such as casein, ovalbumin

• Regulatory proteins like the hormones insulin and glucagon

• Transport proteins like myoglobin and haemoglobin

• Structural proteins like collagen and elastin

• Defense proteins such as the immunoglobulins/antibodies

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 Importance
Most abundant biomolecule in the cell.

Proteins adopt a three-dimensional conformation.

Also known as the native conformation Loss of structure = Loss of biological function

Essential for the biological function of a protein

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 Structure
PRIMARY LEVEL OF
ORGANIZATION

The sequence of amino acids

of the peptide chain and the
number of amino acids
present.

BONDS PRESENT: PEPTIDE

BONDS

from the lecture of Anthony Carpi

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 Structure

Single bonds = Free to rotate and FOLD

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Structure

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 Structure
SECONDARY LEVEL
OF ORGANIZATION

Refers to the folding and/

or spatial arrangements of
amino acid residues in the
linear sequence of a
polypeptide chain.

BONDS PRESENT:
HYDROGEN BONDS

from the lecture of Anthony Carpi

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Secondary Structure:
𝛂-helix
The carbonyl (C=O) group
forms a hydrogen bond
with the amido (N-H) group
of the 4th amino acid (N+4).

The hydrogen bonds are

parallel to the helical axis,
therefore, stabilizing the
structure.

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Secondary Structure:
𝛂-helix
The R-groups point
outward from the helix =
NO STERIC HINDRANCE
for folding (ideally).

Rotation can be clockwise

or counter-clockwise; most
helices in proteins are
almost always clockwise/
right handed.
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 Factors disrupting the helix
stability
• Presence of helix breakers
• Proline
• Rotation around the bond between the N and 𝛂-
carbon is severely restricted (due to the imino
group)
• N has no H to participate in H-bonds
• Glycine
• Has more conformational flexibility due to it’s R-
group
• Supports other conformations (forms in turns,
loops, or bends)

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 Factors disrupting the helix
stability
• Strong electrostatic repulsion
• Proximity of charged groups of the same sign
• Positive: Lysine and Arginine
• Negative: Glutamate and Aspartate

• Steric repulsion
• Crowding — due to the proximity of several bulky side
chains
• Examples: Valine, Isoleucine, Threonine

• Note: Small hydrophobic residues/amino acids are strong

helix formers
• Examples: Alanine, Leucine

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Secondary Structure:
𝜷-pleated sheet
The carbonyl (C=O) group
forms a hydrogen bond with
the amido (N-H) group of the
adjacent chain.

H-bonds are perpendicular to

the peptide chain.

All R-groups extend above or

below the sheet in an
alternating up and down
direction.
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Secondary Structure:
𝜷-pleated sheet Stronger

Parallel Anti-parallel
𝜷 strands run in the 𝜷 strands run in the
same direction, opposite direction,
resulting to bent H- resulting to linear H-
bonds bonds

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 Structure
TERTIARY LEVEL OF
ORGANIZATION

Refers to how an entire protein

molecule is coiled or folded into
its specific three-dimensional
shape due to interaction of the
R-group.

BONDS PRESENT:
DISULFIDE
H-BOND
HYDROPHOBIC INTERACTION
ELECTROSTATIC ATTRACTION
METAL-ION COMPLEXES from the lecture of Anthony Carpi
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MOST proteins have:
H-bonds
Electrostatic attraction
Hydrophobic interactions Non-polar AA

Opposite charged groups

Between side chains of Cysteine

Figure 4.13 Biochemistry, 7th ed.
© 2012 Cengage Learning
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 Examples
Myoglobin and hemoglobin
• (+) Fe (II) ions
• (-) Disulfide bonds

Trypsin and chymotrypsin

• (-) metal ions
• (+) Disulfide bonds

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 Fibrous proteins
• Consists largely of one type of secondary structure
• Function: Structure (Strength and support)
• Examples: Collagen, Keratin
• Most are water insoluble

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 Globular proteins
• Consists of several types of secondary structures
• Function: Metabolic (Catalytic, transport, etc)
• Examples: Enzymes, Hemoglobin
• They are largely water soluble.

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 Structure
QUATERNARY LEVEL OF
ORGANIZATION

Formed by the assembly of

individual polypeptides into a
larger functional cluster.

Subunits:
2 subunits - Dimer
3 subunits - Trimer
4 subunits - Tetramer

BONDS PRESENT:
COVALENT INTERACTIONS
from the lecture of Anthony Carpi
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 Hemoglobin
• Tetramer (2 𝜷 chains and 2 𝜶 chains)
• Grouped into 2 dimers: 𝜶1 𝜷1 and 𝜶2 𝜷2
• Heme group is a porphyrin of Iron.
• Porphyrins are highly stable, versatile molecules
that are able to chelate with several transition
metals.

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 Hemoglobin
• Iron can interact with 6 ligands
• 4 ligands - Nitrogen atoms of the porphyrin ring
• 5th ligand - Imidazole side chain
• 6th ligand - Iron — upon binding oxygen, it is
tilted at a 60º

• Dimer halves (𝜶1 𝜷1 and 𝜶2 𝜷2)

• 2 types of contacts: Packing (do not shift upon
binding oxygen) and Sliding (shifts upon oxygen
binding)

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 Hemoglobin
When oxygen binds:
• Iron is tilted at a 60º
• Dimers rotate 15º relative to each other, resulting to
haemoglobin’s two conformations:
• T (tense or taut) - Deoxygenated form
• Oxygen is only accessible to heme groups of
𝜶 chains (Steric hindrance - stabilized by H-
bonds and interchain electrostatic
interactions)
• R (relaxed) - Oxygenated form
• No steric hindrance, better capacity for
oxygen binding (H-bonds and electrostatic
interactions are broken)

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 Disrupting protein
organization
1. Denaturation
Process by which a protein loses its natural
conformation by disruption of its structural order be it
quaternary, tertiary, or secondary, but never primary.
May be reversible or irreversible

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 Disrupting protein
organization
Denaturating agents include:

1. Heat
Disruption of hydrophobic interactions

2. Detergents
Disruption of hydrophobic interactions
Example: Sodium dodecyl sulfate

3. Urea or Guanidine
Disruption of hydrogen bonding
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 Disrupting protein
organization
Denaturating agents include:

4. Mercaptoethanol
Reduces sulfide bonds

5. Large changes in pH
Alters the electrostatic attractions between side
chains, esp. with the acidic and basic amino
acids.

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 Disrupting protein
organization
2. Hydrolysis
Destruction of the primary structure through
hydrolysis of peptide bonds
Example: Enzymatic hydrolysis

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 References
1. Campbell, M., Farell, S. (2012). Biochemistry 7 Edition.
th

Belmont, CA: Thomson Brooks/Cole.

2. Mauseth, J.D. (2009). Botany: An Introduction to Plant

Biology Fourth Edition. Sudbury, MA: Jones and Bartlett
Publishers, Inc.

3. Nelson, D., Cox, M. (2008). Lehninger principles of

Biochemistry Fifth Edition. New York: W.H. Freeman and
Company.

4. Boyer, R. (2006). Concepts in Biochemistry 3 Edition.

rd

New York: John Wiley & Sons.

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