Essential%20Biochemistry

1
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
2
Importance of Chirality in Biological Systems
(L)-thalidomide is an effective sedative for
expectant mothers while (D)-thalidomide causes
severe birth defects
3
Hydrophobic Amino Acids
Non-polar side chains that interact very weakly
with water.
What type of bonding forces might contribute
significantly for these AAs?
4
Polar Amino Acids
Amino acid side chains readily interact with water
Where might these AAs be located in a
polypeptide?
5
Charged Amino Acids
Always charged under physiological pH
What is the predicted pKa values for these acids
and bases?
6
Ionizible Amino Acids at Physiological pH Values
Thiol group
Cysteine (Cys)
Thiolate anion
Histidine (His)
Imidazolium ion
Are these oxidation/reduction reactions?
7
pKa Values of Ionizable Amino Acids
ca. pKa
3 4 4 6 8 9 10 10 12
8
Disulfide Bond Formation
Polypeptide stabilization Oxidation/reduction
reaction
9
Amino Acid Coupling via Dehydration Synthesis
What is the Nucleophile, Electrophile and Leaving
Group in this reaction?
10
Levels of Polypeptide Organization
11
A polypeptide Primary Structure Amino Acid
Order or Sequence Coding convention N- to
C-terminus from left to right
12
Bond Length Indicates a Hybrid Bond Number of ca.
1.5
C-N single bond 1.45 Å CN double bond 1.25 Å
Peptide resonance
13
Peptide Bond Forms a Planar Unit
Steric hindrance favors trans configuration
14
Rotation in a Polypeptide Restricted to the Ca
Phi Psi
15
Ramachandran Diagram Shows Permitted Angles in
Green
120
- 60
What is phi and psi?
16
a-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 a-helix be
  located?

17
Hydrophobic Strip Formed on the Surface of
alpha-Keratin
18
n 4 Hydrogen-Bonding Scheme for an Alpha Helix
19
Ribbon Depiction of Ferritin an Iron Storage
Protein
20
Beta-Sheet Polypeptide Secondary Structure
Antiparallel
Parallel
Which configuration would be more stable?
21
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 ß-sheet?
What is a favorable environment for beta-sheets
formation?
22
Beta-Sheet Configurations Super-Secondary
Structure
Beta-Barrel
Reverse Turn
Twisted-Sheet
23
CD4 Surface Protein in HIV with Four Similar
beta-Sheet Domains
24
Alpha-Helix Configuration Super-Secondary
Structure

• Common motif in DNA-binding proteins

25
Overall Configuration of a Single Polypeptide
Tertiary Structure
Oxygen Transporter in Muscles Myoglobin
26
Space-Filling Model of Myoglobin

• Polypeptide Amino Acid Distribution charged
  (blue), hydrophobic (yellow) other (white)

Cross-Sectional View
Surface
27
Overall Configuration of Multiple Polypeptides
Quaternary Structure
Ball and Stick
Ribbon Representation

• a-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?

28
Hydrophobicity Scale
Free energy change in transferring from an
organic to aqueous solution
29
Hydrophobic Effect In Protein Folding
Minimizing H2O-nonpolar interactions
30
Protein Folding by Progressive Stabilization of
Intermediates

• All conformations are not sampled
• Exergonic process
• Hydrophobic interactions a major driver
• Chaperonin-assisted protein folding

31
Chapter 4 Problems 1-5, 7, 10, 11, 12, 13, 23,
29, 35, 37, 51, 55 and 57