Amino Acid Structure and Properties

What would be the overall charge of the oligopeptide DDKYEHHQ at physiological pH?

-5

-4

-3

-2

-2→ To calculate the total charge, it is important to identify amino acids that will have either positive or negative charges on their side chains at physiological pH. In the sequence above, there are three negatively-charged amino acids (D, D, and E) and one positively-charged amino acid (K). The rest are predominantly neutral at physiological pH (~7.4) and thus do not contribute to the total charge. As such, the total charge of the peptide will be -3 + 1 = -2.

(It is important to note that histidine (H) is a basic amino acid, but its side-chain pKa is about 6.0, which makes it predominantly uncharged at physiological pH.)

Which of the following is the correct 1-letter code for tryptophan?

R

F
W

Q

W

Which of the following amino acids contains an amide functional group on its side chain?

Arginine

Asparagine

Histidine

Glutamate

Asparagine→ Asparagine is one of the two amino acids that contains an amide group on its side chain, with the second being glutamine. These two are the amide forms of aspartic acid and glutamic acid, respectively.

A newly developed pharmaceutical peptide has the amino acid sequence WYTSRVU. If a missense mutation occurs at the 6th amino acid, which of the following new amino acids would likely have the least impact on the peptide’s efficacy?

L

N

Q

K

L→ The amino acid in the 6th position is valine (V), which has a nonpolar alkane side-chain. As such, a missense mutation would least likely affect the protein function if valine is replaced with an amino acid containing a similar side chain. Leucine only has one extra carbon in its side-chain compared to valine, making them extremely similar, especially compared to the other options.

What is implied by the term “essential” when describing specific amino acids?

They play a major role in the human body

They act as precursors for neurotransmitters

They cannot be synthesized by the human body

They contain R-groups essential for metabolism

They cannot be synthesized by the human body→ Essential amino acids are those that cannot be synthesized by the human body and must be acquired through dietary means. Nine of the twenty amino acids are considered essential, with an additional seven becoming essential under certain conditions.

A novel protein isolated from a bacterium is found to consist of 320 amino acids. Which of the following is the most reasonable estimate of its molecular weight?

3,500 amu

6,400 amu

35,000 amu

64,000 amu

35,000 amu→ The average molecular weight of an amino acid is 110 amu (or 110 Da), which we can estimate as roughly 100 amu for the purposes of initial estimations. With this in mind, we anticipate that the molecular weight of this protein will be slightly greater than 320 × 100 = 32,000 amu.

Which of the following is true of all chiral, naturally occurring amino acids that play a major role in the human body?

They have an R configuration

They have an S configuration

They are D-amino acids

They are L-amino acids

They are L-amino acids

Which amino acid would most likely mark transition points between different motifs of secondary structures?

P

M

F
W

P→ P is the 1-letter code for proline, which is unique because it is the only amino acid that has a cyclic component to its R-group that cyclizes with the amino acid “backbone”. As such, it has a remarkable ability to break up the secondary structure of proteins by introducing so-called “proline kinks.”

Which of the following amino acids contains a sulfur atom in its side chain?

Ala

Met

Ile

Val

Met→ Met is the 3-letter code for methionine, which is one of two amino acids that contain a sulfur atom, the other being cysteine.

Which of the following amino acids is a precursor for serotonin?

Proline

Methionine

Phenylalanine

Tryptophan

Tryptophan

Which of the following amino acids plays an important role in tertiary structures of proteins by forming covalent bonds with other copies of itself?

Glutamine

Cysteine

Tyrosine

Threonine

Cysteine→ This is a structure of cysteine, which is especially important because two cysteine residues can form covalent disulfide bonds. These bridges are a critical part of the tertiary structure in proteins.

All of the following amino acids have an alcohol group in their side-chain EXCEPT:

N

S

T
Y

N

Which of the following amino acids are often sites of phosphorylation?

I. Tyr

II. Ser

III. Thr

IV. Gln

I, II, and III→ Threonine (thr), tyrosine (tyr), and serine (ser) all contain an -OH group in its side-chain and thus are often targeted by phosphorylation and other processes involved in post-translational modifications and signaling.

Which of the following is a true statement regarding basic amino acids?

Lysine is the most basic of all 20 biological amino acids

Arginine contains 2 nitrogen atoms in its side chain

Histidine retains a neutral charge at physiological pH

Basic amino acids cannot be phosphorylated due to repulsion

Histidine retains a neutral charge at physiological pH→ Under physiological conditions, the deprotonated form of histidine—that is, the uncharged form—is predominant. Therefore, histidine is meaningfully basic but is often neutral in the body.

Which of the following amino acids has the lowest side-chain pKa?

K

E
H

R

E→ E is a 1-letter code for glutamic acid, which has an acidic side chain and thus would have a low pKa.

Almost all naturally occurring amino acids that play a major role in the human body are S-amino acids. Which of the following amino acids is the exception to this trend?

Glu

Gln

Cys

Pro

Cys→ While the vast majority of naturally occurring amino acids in the human body are S-amino acids, the two exceptions are glycine (Gly) and cysteine (Cys). Glycine is achiral and thus does not have R or S isomers. Cysteine is another exception due to the position of the sulfur atom on its side-chain, which gives it R stereochemistry.

What would be the overall charge of the oligopeptide AKDEWHR at physiological pH?

-2

0

+1

+2

0→ To calculate the total charge, it is important to identify amino acids that will have either positively- or negatively-charged residues at physiological pH. In the sequence above, there are two negatively-charged residues (aspartic acid (D) and glutamic acid (E)) and two positively-charged amino acids (lysine (K) and arginine (R)). The rest are neutral at physiological pH and thus do not contribute to the total charge. As such, the total charge of the peptide will be -2 + 2 = 0.

Which of the following amino acids possesses a polar side chain?

Gly

Met

Ile

Ser

Ser→ Serine (Ser) contains a hydroxyl group on its side chain, making it by far the most polar of the options presented.

The Tay–Sachs disease can be caused by a E482K mutation, where amino acid E is replaced by amino acid K at position 482. Which of the following best describes the outcome of this mutation?

A polar side chain is replaced by a nonpolar side chain

A basic side chain is replaced by an acidic side chain

An aromatic side chain is replaced by an aliphatic side chaic

A shorter side chain is replaced by a longer side chain

A shorter side chain is replaced by a longer side chain→ In this mutation, glutamic acid (E) is replaced by lysine (K). Lysine’s side chain contains four carbons and an amino group compared to two carbons and a carboxyl group in the glutamic acid side chain. As such, this mutation replaces an amino acid with a shorter side chain with an amino acid with a longer one. It would also be true to note that an acidic side chain is being replaced by a basic one.