Protein Structure and Amino Acids: Study Guide

Study Guide - Smart Notes

Tailored notes based on your materials, expanded with key definitions, examples, and context.

Protein Structure and Amino Acids

Overview of Proteins and Amino Acids

Proteins are fundamental biological macromolecules, comprising about half of a typical cell’s total dry mass. They perform diverse functions, including structural stability, movement, energy harvesting, metabolism, and cellular signaling. Proteins are polymers composed of amino acids, which are linked by peptide bonds to form polypeptide chains. The sequence and chemical properties of amino acids determine protein structure and function.

Amino Acids: The building blocks of proteins, each containing an amino group (–NH2), a carboxyl group (–COO–), a hydrogen atom, and a unique side chain (R group) attached to a central α-carbon.
Chirality: All amino acids (except glycine) are chiral, existing as L- or D-isomers. Only L-amino acids are found in proteins.
Peptide Bonds: Amino acids are covalently joined by peptide bonds, forming polypeptides.

Classification of Amino Acids by R Group Properties

Amino acids are classified based on the chemical nature of their side chains (R groups), which influence their behavior in proteins and in solution.

Nonpolar (Hydrophobic) Side Chains: Contain mostly uncharged C or H atoms; tend to cluster away from water. Examples: Glycine (Gly), Alanine (Ala), Valine (Val), Leucine (Leu), Isoleucine (Ile), Methionine (Met), Proline (Pro), Phenylalanine (Phe), Tryptophan (Trp).
Polar, Uncharged Side Chains: Can form hydrogen bonds; often found on protein surfaces. Examples: Serine (Ser), Threonine (Thr), Tyrosine (Tyr), Asparagine (Asn), Glutamine (Gln), Cysteine (Cys).
Charged Side Chains: Virtually always charged under physiological conditions.
- Acidic (Negatively Charged): Aspartate (Asp, D), Glutamate (Glu, E).
- Basic (Positively Charged): Lysine (Lys, K), Arginine (Arg, R), Histidine (His, H).

Class	Examples	Properties
Nonpolar (Hydrophobic)	Gly, Ala, Val, Leu, Ile, Met, Pro, Phe, Trp	Hydrophobic, found in protein interiors
Polar, Uncharged	Ser, Thr, Tyr, Asn, Gln, Cys	Hydrophilic, can form H-bonds
Acidic (–)	Asp, Glu	Negatively charged at pH 7
Basic (+)	Lys, Arg, His	Positively charged at pH 7

Peptide Bonds and Polypeptide Structure

Peptide bonds are covalent bonds formed via a condensation reaction between the amino group of one amino acid and the carboxyl group of another. This linkage forms the protein backbone, with side chains projecting from the α-carbon atoms.

Peptide Bond: Rigid and planar due to partial double-bond character, restricting rotation.
Polypeptide: A chain of amino acids linked by peptide bonds; has directionality (N-terminus to C-terminus).
Residue: Each amino acid unit within a polypeptide chain.

Determining Net Charge of Amino Acids and Peptides

The net charge of an amino acid or peptide depends on the ionization state of its ionizable groups, which is influenced by the pH of the environment and the pKa values of the groups.

pKa Values: Each ionizable group has a characteristic pKa value (tendency to ionize).
Physiological pH: ~7.4
Rules for Charge Determination:
- If pH < pKa: The group is mostly protonated.
- If pH > pKa: The group is mostly deprotonated.
- Apply this rule to N-terminus, C-terminus, and side chains (Asp, Glu, Tyr, Cys, His, Lys, Arg).

Example: At pH 7, the side chain of Glu (pKa ≈ 4.1) is deprotonated and negatively charged, while the side chain of Lys (pKa ≈ 10.5) is protonated and positively charged.

Levels of Protein Structure

Proteins have four levels of structural organization, each contributing to their final shape and function.

Primary Structure: The linear sequence of amino acids in a polypeptide chain.
Secondary Structure: Local spatial arrangement of the polypeptide backbone, stabilized by hydrogen bonds. Common types include α-helix and β-sheet.
Tertiary Structure: The complete three-dimensional conformation of a single polypeptide chain, including side chain interactions.
Quaternary Structure: The arrangement of multiple polypeptide chains (subunits) in a protein complex.

Glossary of Key Terms

Amino Acid: A small molecule containing an amino group, a carboxyl group, a hydrogen atom, and a unique side chain attached to a central α-carbon.
Peptide Bond: The covalent bond formed between the carboxyl group of one amino acid and the amino group of another.
Polypeptide: A linear chain of amino acids linked by peptide bonds.
Residue: An amino acid unit within a polypeptide chain.
Primary Structure: The sequence of amino acids in a protein.
Secondary Structure: Local folding patterns such as α-helix and β-sheet.
Tertiary Structure: The overall three-dimensional shape of a single polypeptide chain.
Quaternary Structure: The arrangement of multiple polypeptide chains in a protein complex.
R Group (Side Chain): The variable group attached to the α-carbon of an amino acid, determining its unique chemical properties.

Key Equations

Peptide Bond Formation:
Henderson-Hasselbalch Equation (for pH and pKa relationships):

Example Application

Knowing the classification of amino acids helps predict protein folding, stability, and function. For example, hydrophobic amino acids are often found in the interior of globular proteins, while charged and polar residues are typically exposed to the aqueous environment.