Answer to Practice Problem Draw the chemical structure of the tripeptide Ala – Ser – Cys at pH...

Answer to Practice Problem

Draw the chemical structure of the tripeptide Ala – Ser – Cys at pH 7.

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.

3. What is the net, overall charge of this tripeptide at pH 7? __________

4. What is this peptide called using the one-letter code system for amino acids? ______

S

0

ASC

Proteins:Proteins:Three DimensionalThree Dimensional

Structure and FunctionStructure and Function

Figure 4.3

Space-filling model Ribbon diagram

Levels of Protein StructureFigure 4.1

Resonance structure of the peptide bond

Figure 4.5

Planar peptide groups in a polypeptide chainFigure 4.6

Trans and cis conformations of a peptide groupFigure 4.7

Nearly all peptide groups in proteins are in the trans conformation

Rotation in a peptideFigure 4.8

N-C C-C

phi psi

Ramachandran PlotFigure 4.9

Secondary Structureof Proteins

The alpha helixFigure 4.10

The alpha helix

Figure 4.11

An amphipathic alpha helixFigure 4.12

Amphipathic alpha helices are oftenfound on the surface of a protein

Figure 4.13

The beta sheet

Parallel

Figure 4.16

The beta sheet

Parallel

Figure 4.16N

N

N

The beta sheet

Antiparallel

Figure 4.16

The beta sheet

Antiparallel

Figure 4.16N

N

N

The beta sheet.

Side chains alternatefrom one side to another

Figure 4.17

Levels of Protein StructureFigure 4.1

Reverse turnsFigure 4.19

Type I turn Type II turn

Reverse turnsFigure 4.19

Type I turn Type II turn

Tertiary Structureof Proteins

Supersecondarystructures,

often called“motifs”

Figure 4.20

Domain foldsin proteins

Figure 4.25

Figure 4.24

QuaternaryStructure

Figure 4.26

Protein Folding and Stability

How do proteinsfold and unfold?

The information for proteins to fold is contained in the amino acid sequence.

Can proteins fold by themselvesor do they need help?

Protein folding proceeds through intermediates

Intermediates inprotein folding

Figure 4.37

Heating proteins willunfold or “denature”

the molecule.

Figure 4.31

Anfinsen’sprotein folding

experiment

Figure 4.35

A cell can make a biologically active protein of 100 aminoacids in 5 seconds.

If each amino acid could adopt 10 different conformationsthis makes 10100 different conformations for the protein.

If each conformation were randomly sampled in 10-13 secondsit would take 1077 years

Therefore protein folding must not be a random process.

Protein Folding

Energy well of protein folding

Figure 4.36

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 proteinsand prevent them from aggregating. They assist in refolding the proteins before releasing them.

GroEFigure 4.38

Chaperonin-assisted protein foldingFigure 4.39

Three-dimensional structuresof specific proteins

1. Collagen, a fibrous protein

2. Myoglobin and Hemoglobin, O2 binding proteins

3. Antibodies

Collagen is a fibrous proteinfound in vertebrateconnective tissue.

Collagen has a triple helixstructure, giving it strengthgreater than a steel wire of

equal cross section.

Collagen is35% Glycine21% Proline + Hydroxyproline

The repeating unit isGly – X – Pro (HyPro)

The interior of a collagen triple helix is packed with Glycines (red)

4-Hydroxyproline and 5-Hydroxylysine residues

Figure 4.41 and 4.43

Allysine and lysine residues form cross-links in collagen

Figure 4.44

Allysine residues form cross-links in collagen

Figure 4.44

Hemoglobin and Myoglobin bind oxygenFigure 4.46

Protein

HemeHistidines

Red blood cells (erythrocytes)

Myoglobin is monomeric andbinds oxygen in the muscles

Figure 4.44

Protein

HemeHistidines

Hemoglobin is tetrameric andcarries oxygen in the blood

Figure 4.48

Myoglobin is monomeric andbinds oxygen in the muscles

Figure 4.40

Protein

HemeHistidines

O2

Heme

His 93

His 64

Fe2+

Whale MyoglobinFigure 4.51

Oxygen binding curves of hemoglobin and myoglobinPage 124

Y = Fractional oxygen saturation of myoglobinMb = Concentration of myoglobin molecules without bound oxygenMbO2 = Concentration of myoglobin molecules with bound oxygenMb + MbO2 = total concentration of myoglobin molecules

Oxygen binding curves of hemoglobin and myoglobinFigure 4.52

Oxygen binding induces protein conformational changesFigure 4.53

Hemoglobin binds 2,3-Bisphosphoglycerate at an allosteric site.2,3-Bisphosphoglycerate lowers the affinity for oxygen.

Figure 4.54

CO2 and H+ bind to hemoglobin and decrease oxygen affinity.Figure 4.55

Antibodies are proteins of the vertebrate immune system.Antibodies specifically bind to foreign compounds (antigens)

Figure 4.57

Binding of three different antibodies to an antigenFigure 4.59