1. Amino Acids, Peptides, and Proteins

Question 1

1.1 What are the four groups attached to the central (α) carbon of a proteinogenic amino acid?

Answer 1

1. amino group (-NH2)
2. a carboxylic acid group (-COOH),
3. hydrogen atom,
4. R group (Functional Group)

Question 2

1.1 What is the stereochemistry of the chiral amino acids that appear in Eukaryotic proteins?

L or D?
(R) or (S)?

Answer 2

All chiral eukaryotic proteins are L (L or D refers to the side of the hydroxyl group, L means the hydroxyl group is on the left side)

All chiral eukaryotic amino acids are (S), which the exception of Cysteine, because cysteine is the only amino acid with an R group that has higher priority than a carboxylic acid according to the Cagn-Ingold-Prelog rules

The R means Rectus in Latin (means right) and S means Sinister in Latin (means Left). Molecules that rotate the plane polarised light to right is said as R isomer. Molecule that rotate the plane polarised light to left is said as S isomer.

Question 3

1.1 What amino acids are in the following Categories?

Non-Polar, non aromatic (7):

Aromatic (3):

Polar (5):

Negatively Charged/Acidic (2):

Positively charged/Basic (3):

Answer 3

Non-Polar, non aromatic (7): Glycine, Alanine, Valine, Leucine, Isoleucine, Methionine, Proline

Aromatic (3): Tryptophan, phenylalanine, tyrosine

Polar (5): Serine, threonine, asparagine, glutamine, cysteine

Negatively Charged/Acidic (2): aspartate, glutamate

Positively charged/Basic (3): lysine, arginine, histidine

Question 4

1.1 What are the non-polar, non aromatic AA (7):

Answer 4

Non-Polar, non aromatic (7): Glycine, Alanine, Valine, Leucine, Isoleucine, Methionine, Proline

Question 5

1.1 What are the aromatic proteins (3):

Answer 5

Aromatic (3): Tryptophan, phenylalanine, tyrosine

Question 6

1.1 What are the polar proteins (5)?

Answer 6

Polar (5): Serine, threonine, asparagine, glutamine, cysteine

Question 7

1.1 What are the negatively charged, acidic proteins (2)?

Answer 7

Negatively Charged/Acidic (2): aspartate, glutamate

Question 8

1.1 What are the positively charged, basic proteins (3)?

Answer 8

Positively charged/Basic (3): lysine, arginine, histidine

Question 9

1.1 Where do hydrophobic amino acids tend to reside within a protein? What about hydrophilic ones?

Answer 9

Hydrophobic amino acids tend to reside in the interior of a protein, away from the water.

Hydrophilic amino acids tend to remain on the surface of the protein, in contact with the water.

Question 10

Amino acids are amphoteric. Which part is the acidic part and which part is the basic part?

Answer 10

Acidic: carboxylic group
Basic: the amino group

Question 11

What is the pK_a of the amino acid?

Answer 11

It is the pH at which half of the species is deprotonated.

Ionizable groups tend to gain protons under acidic conditions, and lose them under basic conditions.

Question 12

What is the pKa of the amino and carboxylic group on the amino acids?

What is the pKa of most AA without an ioniziable side chain?

Answer 12

Carboxylic group= 2

Amino group= 9

pKa without side chain= 6

Question 13

What are zwitterions?

Answer 13

Zwitterions are essentially dipoles. They have a positively charged end and a negatively charged end, but the charges cancel each other out, so the whole molecule is neutral.

Question 14

What is the isoelectric point and how do you calculate it?

Answer 14

Isoelectric point is the pH value at which the molecule carries no electrical charge or is neutral.

You calculate it by averaging the two closest pKas (Add two closest pKa’s and then divide by 2)

Question 15

On the titration curve, which portion corresponds to the pKa value and what point responds to the isoelectric point.

Answer 15

It is nearly flat at he pKa values, and nearly verticle at the isoelectric (pI) point.

Question 16

For a generic amino acid, NH2CRHCOOH, with an uncharged side chain, what would be the predominant form at each of the following pH values?

1. pH=1
2. pH=7
3. pH= 11

Answer 16

1. pH=1 ⁺NH₃CRHCOOH
2. pH=7 ⁺NH₃CRHCOO^-
3. pH= 11 NH₂CRHCOO^-
4. Because the pH is 1, less than the pKa of 2, none of the protons will be deprotonated
5. There will be one deprotonated part, because it is between 2 and 9. At pKa there is a deprotonation (loss of 1 hydrogen). Here, the first hydrogen to be lost is from the carboxylic group, which is always the first to lose its hydrogen
6. There will be one more deprotonated ion, this time from the amino group. The pKa for this group is around 9. So once above nine (pH=11), you will have this deprotonated. Now you have two hydrogens gone.

Question 17

Given the following pKa values, what is the value of the pI for each of the amino acids listed below:

Aspartic Acid: (pKa1= 1.88, pKa2= 3.65, pKa3= 9.6)

Arginine: (pKa1= 2.17, pKa2= 9.04, pKa3= 12.48)

Valine: (pKa1= 2.32, pKa2= 6.62)

Answer 17

pI= (1.88 + 3.65)/2= 2.77

pI= (9.04 + 12.48)/2= 10.76

pI= (2.32 + 9.62)= 5.97

Question 18

(1.3) What is the difference between an amino acid, a dipeptide, a tripeptide, and an oligopeptide and a polypeptide?

Answer 18

Amino Acid= 1
Dipeptide= 2
Tripeptide =3
Oligopeptide= < 20
Polypeptide = >20

Question 19

(1.3) What molecule is released during the formation of a peptide bond?

Answer 19

a. Water, or H20
b. There is one OH that is lost from the carboxyl group and on hydrogen from the amino group

Question 20

(1.3) If chymotrypsin cleaves at the carbonyl end of phenylalanine, tryptophan, and tyrosine, how many oligopeptides would be formed in enzymatic cleavage of the following molecule with chymotrypsin?

Val − Phe − Glu − Lys − Tyr − Phe − Trp − Ile − Met − Tyr − Gly – Ala

Answer 20

Val – Phe* − Glu − Lys – Tyr* − Phe* − Trp* − Ile − Met – Tyr*** − Gly – Ala

***= bond breakage

4 would be formed, because a single peptide (Phe and Trp in the middle) are not considered oligopeptides on their own.

Question 21

(1.3) What is the N-terminus and what is the C-terminus?

Answer 21

IN a peptide, the N-terminus is the very end with the free amino end, and the C-terminus is the free carboxyl end at the other side of the peptide.

Question 22

(1.3) What molecules and atoms are being changed when a peptide bond forms?

Answer 22

The carboxyl group (-COOH) loses an oxygen and hydrogen and the amino group (NH₃) loses one hydrogens.

Techical: The nucleophilic amino group of one amino acid attacks the electrophilic carbonyl grup of another amino acids.

Question 23

(1.3) Why are amino acids rigid?

Answer 23

Because of resonance.

In other words, the pi bond that is formed can be de-localizable, making it almost a double bond.

Question 24

(1.4) What are the bonds that hold the primary and secondary structure in place (in terms of protein?)?

Answer 24

Primary: Peptide
Secondary: Peptide (by default) and hydrogen bonds

Question 25

**(1.4)** What role does proline serve in the secondary structure?

Answer 25

Proline’s rigid structure causes it to *introduce kinks* in alpha helix's or create turns in beta pleated sheets.

Question 26

**(1.4)** What *type of bond* holds the beta pleats and alpha helixes together, and from where does the bond form?

Answer 26

**Hydrogen bonds** Forms between amino groups and non-adjacent carboxyl groups.

Question 27

**(1.4)** What type of common structure do **alpha helixes** form?

Answer 27

keratin

Question 28

**(1.4)** In **secondary structures**, where is **proline** located?

Answer 28

**Alpha helix**: at the start of the helix, (NOT in the middle, because it would kink it **Beta Pleated Sheets**: at the corners where the sheet turns.

Question 29

**(1.5)** What is the definition of the **tertiary structure**, what types of subtypes are there, and what are the bonds that stabilize them?

Answer 29

Tertiary Structure: - three-dimensional shape of proteins. - Subtypes include hydrophobic interactions, acid-base/salt bridges, and disulfide links. - Stabilizing bonds include: Van der Waals forces, hydrogen bonds, ionic bonds, and covalent bonds.

Question 30

**(1.5)** What is the definition of the **quaternary structure**, what types of subtypes are there, and what are the bonds that stabilize them?

Answer 30

Quaternary Structure: - Interaction between separate subunits of multi-subunit proteins - There are *no specific subtypes*. - Stabilizing bonds are the same as tertiary structures and include **Van der Waals forces**, **hydrogen bonds**, **ionic bonds**, and **covalent bonds**.

Question 31

**(1.5)** What is the primary motivation for hydrophobic residues in a polypeptide to move to the interior of the protein?

Answer 31

Moving hydrophobic residues to the interior of a protein **increases entropy** by allowing water molecules on the surface of the protein to have more possible positions and configurations. This positive ∆S makes ∆G <0, stabilizing the protein.

Question 32

**(1.5)** List **three** different prosthetic groups that can be attached to a protein and name the conjugated protein.

Answer 32

Common prosthetic groups include **lipids**, **carbohydrates** and **nucleic acids**, known as lipoproteins, glycoproteins, and nucleoproteins.

Question 33

**(1.5)** What are two broad classes of proteins?

Answer 33

1. **Fibrous Proteins**: have structures that resemble sheets or long strands 2. **Globular proteins**: myoglobin- tend to be spherical

Question 34

**(1.5)** What is are the type of bond or interaction that holds tertiary structures together? (x4)

Answer 34

1. Hydrophobic interactions 2. acid-base interactions (salt bridges) 3. Hydrogen bonding 4. Sulfide bonds

Question 35

**(1.5)** What primarily drives the structure of tertiary structures?

Answer 35

The tertiary structure of a protein is primarily the result of moving *hydrophobic* amino acid side chains into the *interior* of the protein

Question 36

**(1.5)** What are **disulfide bonds** and what amino acid is responsible for disulfide bonds?

Answer 36

**Disulfide bonds** are responsible for the *tertiary structure* of the proteins. Two **Cysteine** molecules are oxidized and create a covalent bond An example of this is hair.

Question 37

**(1.5)** What is a **molten globule**?

Answer 37

They are *intermediaries* between the secondary structure and the tertiary structure?

Question 38

**(1.5)** What are four reasons why **quaternary structures** are beneficial?

Answer 38

1. They can be *more stable* by reducing the surface are of the protein complexes. 2. They can *reduce the amount of DNA* needed to encode the protein complexes. 3. They can *bring the catalytic sites close together*, allowing for intermediates from one reaction to be directly shuttled to a second reaction. 4. They can *induce cooperativity*, or allosteric effects.

Question 39

**(1.5)** What are **conjugated proteins**?

Answer 39

They are proteins that derive part of its function from covalently attached molecules. From Book: Proteins with covalently attached molecules are termed conjugated proteins. The attached molecule is a prosthetic group and may be a metal ion, vitamin, lipid, carbohydrate or nucleic acid.

Question 40

**(1.5)** What are **prosthetic groups**?

Answer 40

a cofactor or coenzyme that is covalently bonded to a protein to permit its function. Proteins with lipid, carbohydrate, and nucleic acid prosthetic groups are referred to as lipoproteins, glycoproteins, and nucleoproteins

Question 41

**(1.6)** Why are proteins denatured by **heat**?

Answer 41

**Heat**: Heat denatures proteins by *increasing their average kinetic energy*, thus disrupting hydrophobic interactions.

Question 42

**(1.6)** Why are proteins denatured by **solutes**?

Answer 42

**Solutes**: Solutes denature proteins by disrupting elements of secondary, tertiary, and quaternary structure.

Question 43

**(1.6)** What is the definition of **denaturation**?

Answer 43

**Denaturation**: a protein loses its *three-dimensional* structure.