MT6310 | Biochemistry (Lec) UNIT III: Three-Dimensional Structure of Proteins

1st Shiftings | University of Santo Tomas – Medical Technology

OUTLINE Primary Structure

PROTEIN: STRUCTURE AND - Secondary Structure • It refers to the
FUNCTION - Tertiary Structure
sequence of amino
STRUCTURAL - Quaternary Structure
acids in a
ORGANIZATION OF PROTEIN DENATURATION
polypeptide chain
- Primary Structure
(read from the N- to
C-terminal end).
PROTEIN: STRUCTURE AND FUNCTION • It determines the
• Most abundant native
biomolecule in the cell conformation of the
• Adopt a specific three- peptide/protein.
dimensional conformation. Secondary Structure
o Conformation: spatial • It refers to the ordered 3D
arrangement of atoms arrangements in localized
in a protein regions of a polypeptide chain
• This three-dimensional (regular folding)
structure of a protein is • Spatial arrangement of the
called native conformation. atoms in the polypeptide
o Native proteins: chain
proteins in any of their • Formed and stabilized by
functional, folded hydrogen bond between the
conformation. amide proton and carbonyl
o Native conformation is essential for the biological oxygen
function of a protein.
• Loss of structure results in loss of biological function
• Types of Proteins
• For support
• Collagen, elastin • H-bonded arrangement of backbone of the protein is
Catalytic • For hastening biochemical reactions possible due to free rotation of bonds between:
• Amylase o α-C and α-N (phi φ)
Storage • Storage of amino acids o α-C and carboxyl carbon (psi ψ)
• Casein, ovalbumin • Kinds of Secondary structure
Transport • Transport of other substances
• Hemoglobin, protein channels in
cellular membranes
Regulation • For regulation/ coordination of bodily
activities
• Insulin, glucagon
Receptor • Response of cell to external stimuli
• Neuron receptors in nerve cells
Contractile • Movement
• Myosin, actin
Defensive • Protection against disease
• Antibodies
STRUCTURAL ORGANIZATION OF PROTEIN
o α-Helix
• Levels of structural organization of proteins § Spiral structure
o Primary structure § Stabilized by
o Secondary structure intramolecular
o Tertiary structure hydrogen bonds
o Quaternary structure § Structural features:
® C=O of each
peptide bond is
hydrogen bonded
to the N-H of the
fourth amino acid

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 MT6310 | Biochemistry (Lec) UNIT III: Three-Dimensional Structure of Proteins
1st Shiftings | University of Santo Tomas – Medical Technology

away; there are 3.6 aa/turn

® Pitch: 5.4Å
® H-bonds are parallel to helical axis
® All R groups point outward from helix
® Coil of the helix either right-handed
(clockwise) or left-handed (counter-
clockwise)

§ Types of β-Pleated sheet

® Anti-Parallel sheet
Þ β-strands in an anti-parallel sheet run
in opposite directions resulting in
linear H-bonds (stronger)

§ Constraints of Helix Stability

® Presence of helix breakers
Þ Pro:
(1) the rotation around the N-αC bond
is restricted bec it is part of the ring ® Parallel β-sheet
(2) N has no H to participate in H- Þ β-strands in a parallel sheet run in
bonds same direction resulting to bent H-
Þ Gly: bonds (weaker)
(1) has more conformational flexibility o β-bends or reverse bends
due to its R-group § It permits the change in direction (usually
(2) it supports other about 180o) of the peptide chain.
conformations (e.g. coil or bend) § It connects α-helices and β-strands and allow
the polypeptide chain to fold back on itself,
® Electrostatic repulsion (or attraction)
producing compact 3D-conformation.
between successive charged aa residues.
§ H-bond stabilizes the β-bend.
® Bulkiness (steric strain) between adjacent
§ A β-bend is accomplished over 4 aa residues.
R-groups
§ Gly and Pro are frequently part of the β-bends.
Þ However, small hydrophobic residues
(e.g. Ala, Leu) are strong helix formers
o β-Pleated sheet
§ It is formed when 2 or more polypeptides line
up side by side.
§ Stabilized by hydrogen bonds (intrachain or
interchain) of adjacent polypeptide chains
§ Structural features:
® Each β-strand (polypeptide chain in β-
sheet) is extended into a zigzag.
® H-bonds form are adjacent between β- o Random coil
strands. § These are nonrepetitive structures.
® All R groups extend above or below the § An irregular or unique conformation
sheet in an alternating up and down
direction.
® Adjacent β-strands can run in parallel or
anti-parallel
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 MT6310 | Biochemistry (Lec) UNIT III: Three-Dimensional Structure of Proteins
1st Shiftings | University of Santo Tomas – Medical Technology

o structural (strength and

support)
• Example: collagen, keratin
• Most are water insoluble.

Globular • Polypeptide chain folded into

compact, spherical structure
o Other helical structures
• Consists of many types of 2o
structure
• Function
o metabolic (catalytic,
transport, etc.)
• Example: enzymes, hemoglobin
• They are largely water soluble

o Supersecondary Structures
§ Combinations of α and β-strands Quaternary Structure
§ Example: βαβ unit, αα unit, β-meander and • Spatial arrangement of polypeptide subunits.
Greek key • It is formed by the assembly of individual polypeptides
§ Motif: repetitive supersecondary structures (subunit/monomer) into a larger functional cluster.
• Subunits are stabilized by noncovalent interactions
o similar to 3o structure
Dimer • 2 subunits
Trimer • 3 subunits
Tetramer • 4 subunits

Tertiary Structure
• It refers to three-dimensional conformation of the entire
polypeptide.
• Stabilized by numerous interactions between amino
acid side chains.
o Covalent bonds (e.g. disulfide bond between 2
cys)
o H-bonds DENATURATION
o Salt bridges (electrostatic)
• It refers to a change in the native conformation of the
• Hydrophobic interaction protein that disrupts protein function.
• Major classes • Alteration in the environment disrupting the bonds and
Fibrous • Polypeptide chain arranged in forces of interaction that stabilized protein structure
long strands or sheets • Can be caused by
• Consists largely of one type of o High temperature
2o structure o Change in pH
• Function o Change in ionic strength
o Organic solvents (e.g. urea, alcohol)
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 MT6310 | Biochemistry (Lec) UNIT III: Three-Dimensional Structure of Proteins
1st Shiftings | University of Santo Tomas – Medical Technology

o Reducing agents (e.g. performic acid and

mercaptoethanol)
o Detergents
o Salts of heavy metals

REFERENCE
INSTRUCTOR: Francis Jayson Vallesfino
TEXTBOOK: Bettelheim, F. A., Brown, W. H., Campbell, M. K.,
Farrell, S. O., & Torres, O. J. (2016). Introduction to general,
organic, and biochemistry (11th ed.). Australia: Cengage Learning.

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