Protein Structure and Peptide Bond Properties

Flashcards helping students review protein structure levels, peptide bond planar resonance, cis/trans stereochemistry, and formal vs. net peptide charge calculations based on the lecture.

What structural feature allows glycine to be very flexible and rotate freely without significant thermodynamic penalties?

Glycine lacks a distinct R group side chain and only possesses a hydrogen atom.

What are the defining structural and chemical properties of phenylalanine mentioned in the lecture?

Phenylalanine contains a ring structure and is one of the most hydrophobic amino acids.

Which amino acids carry a positive charge at physiological $pH$ due to their high $pKa$ values?

Arginine and lysine.

How is the primary structure of a protein defined and generated?

The primary structure is the amino acid sequence defined by genetic information through transcription and translation.

Why is the primary sequence critical for a protein's ultimate structure and function?

All the information required for a protein to fold into its three-dimensional structure and perform its function is stored within its primary sequence.

What common local structures compose the secondary structure of a protein?

Alpha helices, beta strands, and turns.

How quickly do secondary structures generally form during protein folding?

Secondary structures form quickly, almost instantaneously.

What defines the tertiary structure of a protein?

The unique three-dimensional overall packing structure or fold formed by the assembly of secondary structures.

What is the minimal level of structural organization required for a protein to be functional?

Tertiary structure (also called the native structure).

What is meant by the native structure of a protein?

The specific folded structure that a protein must adopt in order to be functional.

What defines the quaternary structure of a protein?

The assembly of several individual polypeptide chains, each with its unique structure, into a functional multi-subunit complex.

How many subunits assemble to form functional hemoglobin, and what is its role?

Hemoglobin consists of $4$ assembled subunits and functions to carry oxygen in the blood.

How many polypeptide chains make up the protein insulin?

Insulin is composed of $2$ polypeptide chains.

How many total disulfide bonds are present in an insulin molecule?

There are $3$ disulfide bonds in insulin.

What is the primary function of disulfide bonds in small proteins like insulin?

To permanently lock the protein into its correct, stable three-dimensional conformation.

Are strong disulfide bonds the primary driving force for correct protein folding?

No, disulfide bonds maintain structural stability, but they are not the driving force for correct protein folding.

What type of chemical reaction joins two amino acids together to form a peptide bond?

A condensation reaction that eliminates one water molecule.

Which specific atoms form the covalent peptide bond during amino acid condensation?

The carbonyl carbon of one amino acid and the amine nitrogen of the adjacent amino acid.

What structural feature gives a peptide bond its double-bonded character?

Resonance delocalization between the carbonyl double bond ($C=O$) and the adjacent nitrogen lone pair of electrons.

What geometric shape does a peptide bond assume due to its double-bond resonance feature?

A planar structure.

Which specific atoms lie within the same plane in a planar peptide bond unit?

The preceding C_\text{\alpha}, carbonyl carbon, carbonyl oxygen, nitrogen, amine hydrogen, and the next C_\text{\alpha}.

What are the two allowed peptide bond dihedral angles that satisfy its planar geometry?

0^\text{\circ} (cis conformation) and 180^\text{\circ} (trans conformation).

How are the two adjacent C_\text{\alpha} atoms positioned relative to the peptide bond in a trans conformation?

The two C_\text{\alpha} atoms are located on opposite sides of the peptide bond.

How are the two adjacent C_\text{\alpha} atoms positioned relative to the peptide bond in a cis conformation?

The two C_\text{\alpha} atoms are located on the same side of the peptide bond.

Why is the trans conformation thermodynamically more favorable than the cis conformation for most amino acids?

Because steric clash and repulsion between adjacent C_\text{\alpha} groups and side chains are minimized in the trans conformation.

What percentage of standard non-proline amino acid residues adopt the trans conformation in proteins?

Approximately $99\%$ ($19$ out of $20$ amino acids).

What percentage of proline residues are found in the cis conformation in protein structures?

Approximately $30\%$ of proline residues adopt the cis conformation.

Why does proline adopt a cis conformation significantly more often than the other $19$ amino acids?

Proline's unique ring structure causes significant steric clash even in the trans conformation, resulting in a small energy difference between its cis and trans states.

Which three backbone bonds must be evaluated to determine the conformation of a polypeptide chain for each amino acid?

The Nitrogen-$\text{C}_\alpha$ bond, the $\text{C}_\alpha$-carbonyl carbon bond, and the peptide bond.

By default, which termini correspond to the left and right ends when writing a peptide sequence?

The left end represents the amino terminus (N-terminus), and the right end represents the carboxyl terminus (C-terminus).

Which amino acids make up the peptide sequence represented by the single-letter code PEPTIDE?

Proline, Glutamic acid, Proline, Threonine, Isoleucine, Aspartic acid, and Glutamic acid.

What stereochemical configuration must be maintained when drawing standard amino acid residues in a peptide?

The L-configuration.

What general rule determines whether an ionizable group is protonated or deprotonated at a given $pH$?

If $pH < pKa$, the group is protonated; if $pH > pKa$, the group is deprotonated.

What is the $pKa$ value of the ionizable histidine side chain?

$$6.0$$

What is the $pKa$ value of the lysine side chain listed in the lecture reference table?

Approximately $10.5$

What is the $pKa$ value of the cysteine side chain?

$$8.4$$

What is the $pKa$ value of the arginine side chain?

$$12.5$$

What is the $pKa$ value of the aspartate (D) side chain listed in the transcript table?

$$4.01$$

What are the approximate proportions of protonated and deprotonated histidine at physiological $pH = 7.0$ ($pKa = 6.0$)?

Approximately $90\%$ deprotonated (neutral) and $10\%$ protonated (positively charged).

How is the formal charge of a peptide calculated?

By considering only the charge state of the dominant species for each ionizable group at the given $pH$.

How does net charge calculation differ from formal charge calculation for a peptide?

Net charge incorporates fractional charge contributions from minor species if those minor species carry a charge and are significant.

What rule of thumb cutoff determines whether a minor species must be considered in net charge calculations?

If the $pH$ is within or equal to $1$ $pH$ unit of the group's $pKa$ ($|pH - pKa| \le 1$), the minor species must be considered; otherwise, it is negligible.

Why is cysteine's minor deprotonated species considered negligible when calculating net charge at $pH = 7.0$ ($pKa = 8.4$)?

Because the $pH$ of $7.0$ is $1.4$ $pH$ units away from cysteine's $pKa$ of $8.4$, which is greater than the $1$ $pH$ unit cutoff.

What is the formal charge of the peptide sequence CHARGED at $pH = 7.0$?

$$-1$$

What standard $pKa$ value is typically used for the N-terminus amino group in peptide charge calculations?

Approximately $9.5$ (or $9.0$).

What standard $pKa$ value is typically used for the C-terminus carboxyl group in peptide charge calculations?

Approximately $2.0$

Why does an alanine residue contribute zero charge to a peptide regardless of $pH$?

Alanine possesses a simple methyl side chain that lacks an ionizable group.

What is the net charge of the peptide sequence CHARGED at $pH = 6.0$?

$$-0.5$$

What is the percentage and fractional charge contribution of protonated histidine at $pH = 6.01$ ($pKa = 6.0$)?

Approximately $44\%$ protonated, contributing a $+0.44$ charge.

What is the percentage and fractional charge contribution of protonated histidine at $pH = 6.0$ ($pKa = 6.0$)?

Exactly $50\%$ protonated, contributing a $+0.5$ charge.