proteins: amino acid chains dna polymerase from e. coli standard amino acid backbone: carboxylic...
TRANSCRIPT
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
Where might these AAs be located in a polypeptide?
Amino acid side chains readily interact with water
Charged Amino AcidsAlways charged under physiological pH
What is the predicted pKa values for these acids and bases?
Ionizible Amino Acids at Physiological pH Values
Cysteine (Cys)
Histidine (His)
Imidazolium ion
Thiol group
Are these oxidation/reduction reactions?
Thiolate anion
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 ÅC=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
- 60
+120
What is phi and psi?
• What is the environmental condition favorable for a polypeptide to form an alpha helix?
• Where in the polypeptide would an α-helix be located?
α-Helix is a Coiled Polypeptide: Secondary Structure
Hydrophobic Strip Formed on the Surface of alpha-Keratin
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?
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 Backbone
Beta-Sheet Configurations: Super-Secondary Structure
Twisted-Sheet
Beta-Barrel Reverse Turn
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
• Polypeptide Amino Acid Distribution: charged (blue), hydrophobic (yellow) & other (white)
Space-Filling Model of Myoglobin
Cross-Sectional ViewSurface
Overall Configuration of Multiple Polypeptides: Quaternary StructureBall 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