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Proteins: Amino Acid Chains
DNA Polymerase from E. coli
Standard amino acid backbone:
Carboxylic acid group,
amino group,
the alpha hydrogen and
an R group
(L)-alanine, the natural form
Importance of Chirality in Biological
Systems
(L)-thalidomide is an effective
sedative for expectant
mothers while (D)-thalidomide
causes severe birth defects
(L)-
Hydrophobic Amino Acids
Non-polar side
chains that interact
very weakly with
water.
What type of
bonding forces
might contribute
significantly for
these AAs?
Polar Amino Acids
Amino acid side
chains readily
interact with water
Where might these
AAs be located in a
polypeptide?
Charged Amino Acids
Always charged under physiological pH
What is the predicted pKa values for these acids and bases?
Ionizible Amino Acids at Physiological
pH Values
Thiol group
Cysteine (Cys)
Histidine (His)
Thiolate anion
Imidazolium ion
Are these oxidation/reduction reactions?
pKa Values of Ionizable Amino Acids
ca. pKa
3
4
4
6
8
9
10
10
12
Disulfide Bond
Formation
Polypeptide
stabilization
Oxidation/reduction
reaction
Amino Acid Coupling via
Dehydration Synthesis
What is the Nucleophile, Electrophile and Leaving
Group in this reaction?
Levels of
Polypeptide
Organization
A polypeptide Primary Structure:
Amino Acid Order or Sequence
Coding convention: N- to C-terminus from left to right
Bond Length Indicates a Hybrid Bond
Number of ca. 1.5
C-N single bond 1.45 Å
C=N double bond 1.25 Å
Peptide resonance
Peptide Bond Forms a Planar Unit
Steric hindrance favors trans configuration
Rotation in a Polypeptide Restricted to the Cα
Phi
Psi
Ramachandran Diagram Shows
Permitted Angles in Green
+120
- 60
What is phi and psi?
α-Helix is a Coiled Polypeptide: Secondary Structure
• What is the environmental condition favorable for a
polypeptide to form an alpha helix?
• Where in the polypeptide would an α-helix be located?
Hydrophobic
Strip Formed
on the
Surface of
alphaKeratin
n + 4 Hydrogen-Bonding
Scheme for an Alpha Helix
Ribbon Depiction of Ferritin: an
Iron Storage Protein
Beta-Sheet Polypeptide: Secondary Structure
Antiparallel
Parallel
Which configuration
would be more stable?
Beta-Sheet Backbone
Is the distance of 7 Å reasonable?
What do the green spheres represent?
What is the green spheres orientation relative to the β-sheet?
What is a favorable environment for beta-sheets formation?
Beta-Sheet Configurations:
Super-Secondary Structure
Beta-Barrel
Reverse Turn
Twisted-Sheet
CD4 Surface Protein in HIV with
Four Similar beta-Sheet Domains
Alpha-Helix Configuration:
Super-Secondary Structure
• Common motif in
DNA-binding proteins
Overall Configuration of a Single
Polypeptide: Tertiary Structure
Oxygen Transporter in Muscles: Myoglobin
Space-Filling Model of Myoglobin
• Polypeptide Amino Acid Distribution:
charged (blue), hydrophobic (yellow) & other (white)
Surface
Cross-Sectional View
Overall Configuration of Multiple
Polypeptides: Quaternary Structure
Ball and Stick
Ribbon Representation
α-Keratin – primary component of wool, hair and nails
• Parallel alpha double helix with 7 AA 1,4 hydrophobic strip
• Rich in cysteine residues that can form disulfide bridges
• 2 right-handed double helices coil in an anti-parallel fashion
to form a left-handed super-helix: a coiled-coiled protein
• Length of ca.1000 Å
What causes the hardness of the fibrous protein keratin?
Hydrophobicity Scale
Free energy
change in
transferring
from an organic
to aqueous
solution
Hydrophobic Effect In Protein Folding
Minimizing H2O-nonpolar interactions
Protein Folding
by Progressive
Stabilization of
Intermediates
• All conformations are not
sampled
• Exergonic process
• Hydrophobic interactions
a major driver
• Chaperonin-assisted
protein folding
Chapter 4 Problems: 1-5, 7, 10, 11,
12, 13, 23, 29, 35, 37, 51, 55 and 57