2023 FTE2012 Molecules to Materials

Amino acids and Proteins

Week 4 Tutorial
Answers
1. Sketch the general formula of an 𝛼-amino acid (2-amino acid). Identify the four key features. Are
amino acids in proteins D or L?

Key features: protonated amine, deprotonated carboxylate, 𝛼 − 𝐶 atom, and side chain, R.
Amino acids in proteins are always L.

2. What are the three main classes of amino acids and their subclasses? Give an example of each.

Give full name, three-letter code and one-letter code

Non-polar:

Aliphatic – simple alkyl side chain:

Glycine (Gly, G) , alanine (Ala, A), valine (Val, V), leucine (Leu, L), isoleucine (Ile, I), proline

(Pro, P), Methionine (Met, M), [Cysteine (Cys, C)]

Aromatic:

Phenylalanine (Phe, F), Tyrosine (Tyr, Y), Tryptophan (Trp, W), [Histidine (His, H)]

Polar and neutral:

Serine (Ser, S), threonine (Thr, T), asparagine (Asn,N), glutamine (Gln, Q), [histidine (His,

H), cysteine (Cys, C)]

Charged:

Negative (at pH 7):

Aspartic acid/aspartate (Asp, D), glutamic acid/glutamate (Glu, E)

Positive (at pH 7):

Lysine (Lys, K), arginine (Arg, R), [histidine (His, H)]

3. What is the functional group on the side chains of S and T (and Y)?

Hydroxyl groups (-OH)

4. What are the functional groups on the side chains N and Q?

Amide, -C(=O)NH2

5. What are the functional groups of D and E?

Carboxylic acid/carboxylate, -COOH/-COO−

6. What is the functional group of K?

Ammonium ion, -NH3+ i.e. protonated amine

7. What is special about cysteine?

Cysteine Cys-SH can be oxidised to give a covalent disulfide link, Cys-S-S-Cys (cystine)

8. What is meant by an essential amino acid? Give an example of an essential amino acid.

An essential amino acid is one we (as humans) are unable to synthesise. The 9 essential amino
acids are: leucine, Isoleucine, threonine, methionine, tryptophan,

phenylalanine, valine, lysine, & histidine.

9. Sketch a peptide bond.

If you included the carbon atoms either side, that is fine.

10. What are key features of a peptide bond?

• Partial double bond, due to electron delocalisation.

• Restricted rotation (due to partial double bond character)

• Two stable conformations, cis and trans.

11. What are the four levels of protein structure and their key characteristics?

• Primary structure – sequence of amino acids

• Secondary structure -- 𝛼-helices, 𝛽-sheets, 𝛽-turns

 • Tertiary structure – the stable folded conformation of 𝛼-helices, 𝛽-sheets,, turns and

loops

• Quaternary structure – the association of subunits into dimers, trimers, tetramers,.....

Homo-oligomer – identical subunits (e.g., 𝛽-lactoglobulin)

Hetero-oligomer – non-identical subunits (e.g., adult hemoglobin)

12. Are side chains involved in forming secondary structure elements?

No, they are not directly involved. Secondary structure elements of -helices and -sheets

involve hydrogen bonding of the peptide groups only.

13. Do side chains play any role in determining secondary structure elements?

Yes!!

A pattern of 2-3 successive hydrophilic side chains followed by 3-2 hydrophobic side chains is

a signature of an 𝛼-helix for a water-soluble protein.

A pattern of alternating hydrophobic and hydrophilic residues is a signature of a -strand for

a water-soluble protein.

14. For a membrane-bound protein, what sort of residues would you expect to line the stripe

facing the membrane?

The phospholipid bilayer that forms cellular membranes has hydrophobic tails. One would

expect the membrane-facing part of the helix to be lined with hydrophobic residues.

15. Identify which peptide bonds have a cis and which have a trans configuration:

cis, cis, trans

16. Sketch a salt bridge between a pair of amino acid side chains.

17. Sketch a hydrogen bond between a pair of neutral side chains.

18. Which interaction is a long-range interaction and which is a short range? How does energy of

interaction vary with distance.

Salt bridges are long- range interactions. Strength/energy of interaction in Joules varies as

1/R, where R is the distance between charge centres.

London (dispersion) interactions are short range. Strength/energy of interaction in Joules

varies as 1/R6.

19. A methane molecule approaches a binding pocket on an enzyme where at a distance of 3.6

Å (0.36 nm) the strength of interaction is -2.56 kJ/mol. At a distance of 7.2 Å (0.72 nm) what

is the energy of the interaction?

The ratio of distances is 2.0, so the energy of interaction is (-2.56 kJ/mol)/26 ≅ 0.04 kJ/mol.

20. A protein has many prolines and glycines in its structure. Would you expect it to form 𝛽-

sheets and α -helices?

No: a proline can only form a hydrogen bond with another peptide group through its

carbonbyl (-C=O) group. Glycine without a bulky side -CH3 or -CH2- attached at the C is

conformationally flexible.

21. A water-soluble protein has many charged side chains. Would you expect it to fold into a

stable 3D structure?

No. For proteins to fold there has to be a good number (~50%) of hydrophobic residues to

form the core of the protein. The energy of protein-water interactions is greater than the

energy of protein-protein interactions.

23. What are some physical ways of denaturing a protein?

Temperature, pressure, shear

24. Glutathione -- found in high abundance in many foods. Important antioxidant.

(a) What amino acids comprise glutathione?

 𝛾-Glutamic acid/glutamate, cysteine, glycine

(b) Identify the peptide bonds.

(c) Is there one peptide bond that is not the standard peptide bond between an 𝛼-

carboxylic acid and an 𝛽-amino group?

Yes, the first peptide linkage is between the carboxylic acid side chain of glutamic acid and the
𝛼-amino group of cysteine. Alternatively (and probably more correctly) we have a standard
peptide linkage the 𝛼-amine of cysteine, and the 𝛼-carbon of 𝛾-glutamic acid (i.e. the amine of
glutamic acid is on the 𝛾-carbon and not the 𝛼-carbon.

Proper name: γ-L-Glutamyl-L-cysteinylglycine

(d) Glutathione is a key antioxidant. The ratio of reduced form to oxidised form is a mark of

cellular oxidative stress. Reduced to oxidised should be ~9:1. What is the oxidised form

of glutathione? [Hint: think cysteine]

o
Abbreviated: 2 GSH → GSSG + 2 H+ + 2 e− 𝐸cell = −0.24 V