Lecture 4

Overview of Protein Structure and Amino Acids

Understanding protein structure begins with a solid foundation in amino acids, which are the fundamental building blocks of proteins. This overview highlights the diversity and complexity of amino acids, their classifications, and their significance in biological processes.

Amino Acid Basics

Proteins are primarily composed of 20 common amino acids, each of which contributes unique qualities to protein structure and function. Each amino acid is characterized by four key components:

• An amino group (–NH₂) that acts as a base.

• A carboxyl group (–COOH) that acts as an acid.

• A hydrogen atom.

• A variable side chain (R group) that determines the specific properties and classification of the amino acid.

Amino Acid Classifications

Aliphatic and Aromatic Amino Acids

• Aliphatic Amino Acids: These have nonpolar side chains, such as valine and leucine, which are typically found in the protein's interior, contributing to hydrophobic interactions that stabilize protein folding.

• Aromatic Amino Acids: These have side chains containing aromatic rings and can vary in polarity.

  • Phenylalanine (F, PG): This amino acid has a simple structure featuring a bulky hydrophobic benzene ring, making it critical for protein structure maintenance.

  • Tryptophan (TRP, W): Bulkier than phenylalanine, it contains a nitrogen atom in its ring structure, influencing protein interaction with various ligands.

  • Tyrosine (Tyr, Y): Featuring a phenolic alcohol group (–OH), it is polar and versatile; it can engage in hydrogen bonding and act as a weak acid, playing critical roles in enzyme active sites.

Polar Amino Acids

• Serine (Ser, S): A simple polar amino acid that possesses a hydroxyl (–OH) functional group, enhancing its reactivity and ability to participate in enzymatic processes.

• Threonine (Thr, T): Slightly bulkier than serine due to a methyl group, threonine's properties can play interchangeable roles in protein structures based on specific environmental contexts and evolutionary adaptations.

Amino Acids with Sulfur

• Cysteine: Contains a sulfur atom (–SH) and has a polar side chain, allowing it to form crucial disulfide bonds and cross-links within proteins, which are pivotal for protein folding and stability in extracellular environments.

• Methionine (Met, M): This amino acid features a thioether group and, while primarily nonpolar, has the potential for slight polar behavior, participating in various metabolic processes.

Charged Amino Acids

• Basic Amino Acids: These amino acids are positively charged at physiological pH and include:

  • Histidine (His, H): Contains an imidazole ring, making it capable of proton acceptance, thus acting as a weak base essential in enzyme active sites and buffering systems.

  • Lysine (Lys, K): Features a long chain of methylene groups ending in a terminal amino group, resulting in strong positive charge at physiological pH, contributing to interactions with negatively charged molecules.

  • Arginine (Arg, R): Similar to lysine but has additional nitrogen atoms in its side chain, ensuring a strong positive charge at physiological pH, influencing its interaction with other molecules significantly.

• Acidic Amino Acids: These amino acids contain carboxyl groups that lose protons at physiological pH, resulting in a net negative charge. This group includes:

  • Aspartate (Asp, D): Differing from glutamate by one less methylene group, playing roles in neurotransmission and metabolism.

  • Glutamate (Glu, E): Longer than aspartate, it fulfills numerous functions in proteins and neurotransmitter signaling, depending on the structural requirements of the protein.

Protein Interactions and Modifications

The modification of amino acids can significantly influence protein structure and function. These modifications include:

• Hydroxylation, methylation, and phosphorylation, which often affect stability, activity, and interactions of proteins.

  • 4-Hydroxyproline: Essential in collagen biosynthesis; it is synthesized from proline specifically in the presence of vitamin C, linking nutritional deficiencies to collagen-related health issues.

  • Gamma-carboxyglutamate: This modification affects glutamic acid and is crucial for blood coagulation processes.

Peptide Bond Formation

Amino acids connect via peptide bonds (amide bonds) formed through condensation reactions, resulting in the loss of water. These bonds contribute to the proteins’ directional polarity, characterized by an N-terminus (amino end) and a C-terminus (carboxyl end).

Structural Characteristics of Proteins

• Peptide Bonds: These bonds have partial double bond characteristics, restricting rotation and introducing rigidity, which is essential for maintaining protein architecture.

• Folding: Protein structure is primarily determined by the nature and sequence of amino acid side chains, which dictate folding patterns. The flexibility around the peptide bonds is described by Phi (φ) and Psi (ψ) angles, highlighting the complex conformational landscapes proteins can adopt. The trans configuration of peptide bonds is preferred over the cis configuration due to steric hinderance, further influencing protein stability.

Importance of Sulfur Bonds

• Disulfide Bonds: Formed between cysteine residues, these bonds significantly enhance protein stability, particularly under oxidative conditions often encountered in extracellular environments.

Isoelectric Point

The isoelectric point (pI) of an amino acid is critical, as it represents the pH at which the molecule has no net charge, making it the least soluble in solution. Understanding charge changes based on pH is vital for predicting behavior in physiological conditions, impacting solubility, enzyme activity, and molecular interactions.

Amino Acid Properties Summary

Amino acids differ significantly in:

• Polarity: Altering solubility and interaction patterns in different environments.

• Solubility: Influenced by pH levels, affecting the behavior of proteins in varying ionic environments.

• Charge Status: Determines interactions with other molecules and overall protein functionality.

• Structural Flexibility: Governed by the types of side chains, allowing diverse protein structures and functions.

Practical Applications

A comprehensive understanding of amino acids and their properties is essential for:

• Predicting protein structure and function: Facilitating insights in biochemistry and molecular biology.

• Utilizing knowledge in biotechnology and drug design: Innovating new therapeutic solutions that target specific protein interactions and modifications to treat diseases effectively.