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Answer to Practice Problem
Draw the chemical structure of the tripeptide Ala – Ser – Cys at pH 7.
S
Answer the following with regard to this tripeptide:
1. Indicate the charge present on any ionizable group(s).
2. Indicate, using an arrow, which covalent bond is the peptide bond.
0
3. What is the net, overall charge of this tripeptide at pH 7? __________
ASC
4. What is this peptide called using the one-letter code system for amino acids? ______
Proteins:
Three Dimensional
Structure and Function
Space-filling model
Figure 4.3
Ribbon diagram
Levels of Protein Structure
Figure 4.1
X-ray crystallography is used to determine protein structure
Figure 4.2
Resonance structure of the peptide bond
Figure 4.5
Planar peptide groups in a polypeptide chain
Figure 4.6
Trans and cis conformations of a peptide group
Figure 4.7
Nearly all peptide groups in proteins are in the trans conformation
phi
N-Ca
psi
Ca-C
Rotation in a peptide
Figure 4.8
Ramachandran Plot
Figure 4.9
Secondary Structure
of Proteins
The alpha helix
Figure 4.10
The alpha helix
Figure 4.11
An amphipathic alpha helix
Figure 4.12
Amphipathic alpha helices are often
found on the surface of a protein
Figure 4.12
The beta sheet
Parallel
Figure 4.15
The beta sheet
Parallel
Figure 4.15
N
N
N
The beta sheet
Antiparallel
Figure 4.15
The beta sheet
Antiparallel
Figure 4.15
N
N
N
The beta sheet.
Side chains alternate
from one side to another
Figure 4.16
Levels of Protein Structure
Figure 4.1
Reverse turns
Figure 4.18
Type I b turn
Type II b turn
Reverse turns
Figure 4.18
Type I b turn
Type II b turn
Tertiary Structure
of Proteins
Supersecondary
structures,
often called
“motifs”
Figure 4.19
Domain folds
in proteins
Figure 4.23
Figure 4.24
Quaternary
Structure
Figure 4.25
Protein Folding and Stability
How do proteins
fold and unfold?
The information for proteins to
fold is contained in the
amino acid sequence.
Can proteins fold by themselves
or do they need help?
Protein folding proceeds through intermediates
Intermediates in
protein folding
Figure 4.31
Heating proteins will
unfold or “denature”
the molecule.
Figure 4.25
Anfinsen’s
protein folding
experiment
Figure 4.29
Protein Folding
A cell can make a biologically active protein of 100 amino
acids in 5 seconds.
If each amino acid could adopt 10 different conformations
this makes 10100 different conformations for the protein.
If each conformation were randomly sampled in 10-13 seconds
it would take 1077 years
Therefore protein folding must not be a random process.
Energy well of protein folding
Figure 4.25
Forces driving protein folding:
1. Hydrophobic effect
2. Hydrogen bonding
3. Charge-charge interactions
4. Van der Waals interactions
Molecular Chaperones
(Chaperonins)
Some proteins don’t spontaneously fold to native structures.
They receive help from proteins called chaperonins
Best characterized chaperonin system is from E. coli.
GroEL / GroES chaperonin system (GroE chaperonin)
These chaperonins bind to unfolded or partially folded proteins
and prevent them from aggregating. They assist in
refolding the proteins before releasing them.
GroE
Figure 4.32
Chaperonin-assisted protein folding
Figure 4.33
Three-dimensional structures
of specific proteins
1. Collagen, a fibrous protein
2. Myoglobin and Hemoglobin, O2 binding proteins
3. Antibodies
Collagen is a fibrous protein
found in vertebrate
connective tissue.
Collagen has a triple helix
structure, giving it strength
greater than a steel wire of
equal cross section.
Collagen is
35% Glycine
21% Proline + Hydroxyproline
The repeating unit is
Gly – X – Pro (HyPro)
The interior of a collagen triple helix is packed with Glycines (red)
4-Hydroxyproline and 5-Hydroxylysine residues
Figure 4.34 and 4.37
Allysine and lysine residues form cross-links in collagen
Figure 4.38
Allysine residues form cross-links in collagen
Figure 4.38
Hemoglobin and Myoglobin bind oxygen
Figure 4.40
Heme
Histidines
Protein
Red blood cells (erythrocytes)
Myoglobin is monomeric and
binds oxygen in the muscles
Figure 4.40
Heme
Histidines
Protein
Hemoglobin is tetrameric and
carries oxygen in the blood
Figure 4.40
Myoglobin is monomeric and
binds oxygen in the muscles
Figure 4.40
Heme
Histidines
Protein
His 64
Fe2+
O2
Heme
His 93
Whale Myoglobin
Figure 4.45
Oxygen binding curves of hemoglobin and myoglobin
Page 117
Y = Fractional oxygen saturation of myoglobin
Mb = Concentration of myoglobin molecules without bound oxygen
MbO2 = Concentration of myoglobin molecules with bound oxygen
Mb + MbO2 = total concentration of myoglobin molecules
Oxygen binding curves of hemoglobin and myoglobin
Figure 4.46
Oxygen binding induces protein conformational changes
Figure 4.47
Hemoglobin binds 2,3-Bisphosphoglycerate at an allosteric site.
2,3-Bisphosphoglycerate lowers the affinity for oxygen.
Figure 4.48 and 4.49
CO2 and H+ bind to hemoglobin and decrease oxygen affinity.
Figure 4.50
Antibodies are proteins of the vertebrate immune system.
Antibodies specifically bind to foreign compounds (antigens)
Figure 4.52
Binding of three different antibodies to an antigen
Figure 4.54