Amino Acids, Peptides, and Protein Structures

Nonpolar Amino Acids

*Glycine* [Aliphatic] *Alanine* [Aliphatic] *Valine* [Aliphatic] *Leucine* [Aliphatic] *Isoleucine* [Aliphatic] *Methionine*[Aliphatic] *Phenylalanine* {Aromatic] *Tryptophan* [Aromatic] *Proline* [Aliphatic]

Three Basic Amino Acids

*Lysine* *Arginine* *Histidine*

Polar Amino Acids

*Serine* *Threonine* *Cysteine* *Tyrosine* *Asparagine* *Glutamine*

At their isoelectric point proteins exhibit which of the following? A. no ionized groups. B. no positively charged groups. C. no negatively charged groups. D. all of their acidic groups protonated. E. no tendency to migrate in an electric field.

E

Structure levels of proteins

*Primary* - sequence of amino acids *Secondary* - hydrogen bonding/interactions *Tertiary* - side-chain interactions *Quaternary* - behavior of subunits coming together

Aspartate

- Acidic - Electrically charged side-chain *(D) Asp*

Glutamate

- Acidic - Electrically charged side-chain *(E) Glu*

Alanine

- Aliphatic - Nonpolar side-chain *(A) Ala*

Proline

- Aliphatic - Nonpolar side-chain *(P) Pro*

Isoleucine

- Aliphatic - Nonpolar side-chain - An essential amino acid *(I) Ile*

Choose the best answer concerning the amino acid cysteine. A. It is required for the formation of tertiary structure in proteins. B. It can be present within the active site of enzymes and function as a nucleophile. C. It forms disulfide bonds in secreted proteins. D. The side-chain thiol has a pK of 6.5. E. Both A and C F. Both B and C

F

Two Acidic Amino Acids

*Aspartate* *Glutamate*

Glycine

- Aliphatic - Nonpolar side-chain - *Not chiral* *(G) Gly*

Fischer Projection for amino acids

Key things to remember: - With fischer projections, hydrogen on the left or right arms necessitate the chriality to be read 'backwards' - The carboxyl group and R-group will always be on the top and bottom respectively of the fischer projection - To change the configuration of an amino acid in the presented fischer projection, simply swap the position of the amino group and the hydrogen

Salt Bridges

Impact the tertiary structure of proteins. A combination of two noncovalent interactions: hydrogen bonding and electrostatic interactions. These noncovalent interactions improve the overall stability of a polypeptide chain.

Peptides and proteins are formed by connecting amino acids with *peptide bonds*.

Peptide bonds utilize a type of amide bond that has planar geometry. This is due to the resonance within the structure- allowing for the nitrogen to double bond. This causes the nitrogen to sp² hybridize and present with planar molecular geometry. With the existence of resonance, there is no rotation about the amide bond. However, the phi and psi bonds extending outside the amide bond can rotate.

The 9 essential amino acids

his, leu, ile, lys, met, phe, thr, trp, and val *K*iss *M*y *L*ucky *T*oes *F*or *V*ast *W*ealth *I*s *H*ere. Given this name as these are amino acids that the body needs but cannot produce on its own; thus, getting these amino acids from the diet is essential for regular physiological function.

Leucine

- Aliphatic - Nonpolar side-chain - An essential amino acid *(L) Leu*

Valine

- Aliphatic - Nonpolar side-chain - An essential amino acid *(V) Val*

Methionine

- Aliphatic - Nonpolar side-chain - While there is sulfur found in the R-group, this amino acid cannot form disulfide bonds - An essential amino acid *(M) Met*

Hydrophobic vs Hydrophilic Interactions

Impact the tertiary structure of proteins. *Hydrophobic interactions* occur when amino acids with nonpolar, hydrophobic R groups cluster together on the inside of the protein, leaving hydrophilic amino acids on the outside to interact with surrounding water molecules.

Quaternary [protein structure]

Occurs when multiple polypeptide subunits come together. This is not seen in all proteins. Examples of proteins with quarternary structure are hemoglobin and DNA polymerase.

Phenylalanine

- Aromatic - Nonpolar side-chain - An essential amino acid *(F) Phe*

Arginine

- Basic - Electrically charged side-chain *(R) Arg*

Disulfide Bonds

Impact the tertiary structure of proteins. Covalent linkages between the sulfur-containing side chains of *cysteines*; much stronger than the other types of bonds that contribute to tertiary structure. Act like molecular "safety pins," keeping parts of the polypeptide firmly attached to one another.

Tryptophan

- Aromatic - Nonpolar side-chain - An essential amino acid *(W) Trp*

Cysteine

- Polar side-chain - Naturally found as the d-isomer due to the attached sulfur altering the chirality - Can form *disulfide bonds* *(C) Cys*

Uncommon Amino Acids

In addition to the 20 common amino acids, there are also several uncommon amino acids in the body- these occur post-translationally. - *Hydroxylysine* and *hydroxyproline*. These are found in the protein collagen. Collagen is a fibrous protein made up of three polypeptides that form a stable assembly, but only if the proline and lysine residues are hydroxylated (a hydroxy group is added) - *Thyroxine*, an iodinated derivative of tyrosine, found in thyroglobulin (produced by thyroid gland) - *g-carboxyglutamic acid* (i.e. glutamic acid with two carboxyl groups) found in certain blood clotting enzymes

Protein

A biological macromolecule of molecular weight 5000 g/mol or greater, consisting of one or more polypeptide chains

Basic Amino Acid Structure

Made up of the following : *an alpha carbon, hydrogen, an amino group, a carboxyl group, and a structurally unique R-group* Most are chiral and naturally found in the l-isomer formation.

*What stage of protein synthesis does NOT require energy?* Initiation Elongation Termination All stages of protein synthesis require energy.

[D] is the correct answer. All three stages of protein synthesis (initiation, elongation, and termination) require large amounts of energy.

Histidine

- Basic - Electrically charged side-chain - An essential amino acid *(H) His*

Lysine

- Basic - Electrically charged side-chain - An essential amino acid *(K) Lys*

Asparagine

- Polar side-chain *(N) Asn*

Glutamine

- Polar side-chain *(Q) Gln*

Serine

- Polar side-chain *(S) Ser*

Tyrosine

- Polar side-chain *(Y) Tyr*

Threonine

- Polar side-chain - An essential amino acid *(T) Thr*

Collagen contains large amounts of which of the following? A. Inter-chain hydrogen bonds B. Intra-chain hydrogen bonds C. ß-sheet D. α-helix E. 310 -helix

A

Which of the following amino acid substitutions most likely causes a change in a protein's tertiary structure? A. Isoleucine to arginine B. Arginine to lysine C. Valine to leucine D. Threonine to serine E. Asparagine to glutamine

A

Which sequence of atoms can be found in the backbone of polypeptides? A. C-C-N-C B. N-C-C-C C. C-O-C-N D. C-N-N-C E. C-C-C-N

A

Polypeptide

A macromolecule containing many amino acids joined by peptide bonds

Tripeptide

A molecule containing three amino acids joined by peptide bonds

Dipeptide

A molecule containing two amino acids joined by a peptide bond

Amphoteric

A molecule or ion that can react both as an acid as well as a base. Amino acids are amphoteric. This distinction allows for the existence of the protein buffer system in the body.

Peptide

A short polymer of amino acids joined by peptide bonds (about 2-50)

Isoelectric point

Also known as the pI. This is the pH where the amino acid has no net charge. Amino acids can appear in three forms: their cationic form, neutral, and anionic form.

Which of the following groups of amino acids would be characterized as entirely hydrophobic? A. His, Gly, Ala B. Phe, Ile, Val C. Trp, Glu, Val D. Asn, Glu, Arg E. Asp, Ser, Phe

B

Which of the following is most responsible for the maintenance of protein secondary structure? A. Hydrophobic interactions B. van der Waals forces C. Hydrogen bonds D. Disulfide cross-links E. Salt bridges

C

At physiological pH, lysine (pK amino group = 9.0; pK carboxylate group = 2.2; pK of ionizing side-chain = 10.5) would exist mainly as a species with a net charge of which of the following? A. -2 B. -1 C. 0 D. +1 E. +2

D

Given the following 5 amino acids, which of them is the most hydrophilic at pH 7.0? A. serine B. asparagine C. methionine D. arginine E. glycine

D

In a multisubunit protein such as hemoglobin, the individual polypeptide chains are usually bound to one another by all of the following EXCEPT for which one? A. hydrogen bonds B. electrostatic interactions C. hydrophobic interactions D. peptide bonds

D

The primary structure of the collagen alpha-chain is best represented by which of the following? [X, Y, and Z represent any amino acid and n=250-400.] A. (X-Gly)n B. (Pro-Y-Z)n C. (Lys-Pro-Z)n D. (X-Y-Gly)n E. (Gly-X-Y-Pro)n

D

Which of the following is directly responsible for initiation of triple helix formation during procollagen biosynthesis? A. deamination of lysine residues to form an aldehyde group and formation of crosslinks. B. intra-peptide disulfide bond formation in the N- terminal pro-peptide of procollagen. C. hydroxylation of lysine residues in the procollagen protein. D. inter-peptide disulfide bond formation between C- terminal pro-peptides of procollagen. E. removal of cross-linked C- terminal pro-peptides in mature collagen.

D

Which of the following statements is TRUE for collagen? A. The fundamental collagen polypeptide is an alpha-chain that forms alpha-helices. B. Collagen fibrils are formed by the self-assembly of procollagen molecules. C. The carbohydrate residues are bound to hydroxyproline. D. Glycine makes up nearly one third of the amino acid residues. E. Arrangement of collagen fibrils is determined by the presence of alanine.

D

Given the following 5 amino acids, which has the bulkiest side chain? A. alanine B. valine C. tyrosine D. histidine E. tryptophan

E

Tertiary [protein structure]

The 3-D folding pattern of a polypeptide that results from the side-chain (or R-group) interactions. There are multiple R-group interactions that can impact the overall tertiary structure. These are: salt bridges, hydrogen bonds, disulfide bonds, and the hydrophobic and hydrophilic interactions.

Primary [protein structure]

The sequence of amino acids in the polypeptide.

Which of the following statements is TRUE for proline and hydroxyproline in collagen? A. Hydroxylation occurs on the collagen protein after synthesis on the ribosome B. Proline in native collagen results from dehydroxylation of hydroxyproline C. Collagen is not synthesized on ribosomes permitting direct insertion of hydroxyproline D. Hydroxylation of proline occurs on the prolyl-tRNA E. There are separate codons for hydroxyproline and proline

A

*Which of the following amino acids would most likely be found in the transmembrane portion of the NMDA receptor?* (A) Leu (B) Pro (C) Arg (D) Asn

A Proteins that span the plasma membrane must contain hydrophobic (nonpolar) amino acid residues in the transmembrane region. Of the amino acids listed, only leucine and proline are nonpolar; arginine and asparagine are both polar (choices C and D can be eliminated). Proline, while nonpolar, does not fit well into the alpha helical shape of most transmembrane regions, making leucine the more likely of the two to be found there (choice B can be eliminated, and choice A is correct).

Secondary [protein structure]

The local folded structures that form within a polypeptide due to interactions between atoms of the backbone- that is, the folding occurring without the involvement of the R-groups. These interactions typically take the form of hydrogen bond interaction between an amino acid's carbonyl group and the amino group of another amino acid. The most common secondary structures are the *α helix* and the *β pleated sheet*. α helix structures pull the polypeptide into a helical structure- where the R-groups stick out of the helix and are free to interact. β pleated sheet structures form sheet-like structures where the R-groups extend above and below the plane of the sheet. Strands can be parallel (where the N and C termini line up) or antiparallel (where the N and C termini are next to each other). Antiparallel beta pleated sheets are more stable than their parallel cousins. Amino acids that prefer to form α helix are: Alanine, Leucine, Methionine, Phenyalanine, Glutamine, Glutamate, Histidine, and Arganine. Amino acids that prefer to form β pleated sheet are: Tyrosine, Tryptophan, Pheylalanine, Methionine, Isoleucine, Valine, Threonine, and Cysteine.