Amino Acid Side Chains Properties

Amino Acid Side Chains

• Proline has a primarily aliphatic character, but is frequently found on protein surfaces due to its unique structural constraints.
• The rigid ring of proline is well-suited to protein sites where the protein must fold back on itself (turns).
• Methionine and tyrosine are fairly hydrophobic, but display more hydrophilic character than their aliphatic analogs.
• The –OH group of serine and the –SH group of cysteine are good nucleophiles and often play key roles in enzyme activity.

Cysteine

• The side chain has a pKa = 8.3, so it can ionize at moderately high pH.
• The oxidation of two cysteine side chains yields a disulfide bond, producing cystine.

Hydrophobic Amino Acids

• Phenylalanine is one of the most hydrophobic amino acids.
• Tyrosine and tryptophan have some hydrophobic character, but it is tempered by the polar groups in their side chains.

Aromatic Amino Acids

• Aromatic amino acids absorb light in the near-ultraviolet region of the spectrum.
• This characteristic is frequently used for protein detection and/or quantitation by measuring absorption at 280 nm.

Basic Amino Acids

• Lysine (pKa = 10.0) and arginine (pKa = 12.5) are the most basic amino acids.
• Their side chains are almost always positively charged under physiological conditions.
• The guanidino group of arginine makes it the most basic amino acid due to resonance stabilization of the protonated side chain.

Acidic Amino Acids

• Aspartic acid (pKa = 3.9) and glutamic acid (pKa = 4.2) typically carry negative charges at pH 7.
• These amino acid residues are often referred to as aspartate and glutamate (conjugate bases rather than acids).
• Asparagine and glutamine have uncharged polar side chains, and are hydrophilic, tending to be on the surface of a protein molecule.

Post-translational Modification

• Amino acids can undergo post-translational modification, resulting in modified amino acids with unique properties.

Peptides and the Peptide Bond

• Amino acids can be covalently linked together by formation of an amide bond between the α-carboxylic acid group on one amino acid and the α-amino group on another.
• This bond is often referred to as a peptide bond, and the products formed by such a linkage are called peptides.
• A peptide composed of 2 amino acids is called a dipeptide, and a peptide composed of 4 amino acids is called a tetrapeptide.
• The amide bond formation leaves an amino group available on one end of the tetrapeptide and a carboxylate group on the other, called the N-terminus and C-terminus, respectively.

Secondary Structure

• The p-helix is a type of secondary structure found in ~15% of protein sequences in the Protein Data Bank.
• It is also known as an “α-bulge” or “p-bulge” and occurs only once in any given sequence.
• The p-helix conformation is created by the insertion of an amino acid into an α-helix, resulting in a bulge in the helical structure.

Fibrous Proteins

• Fibrous proteins have a filamentous, or elongated, form.
• They play structural roles in animal cells and tissues and include the major proteins of skin and connective tissue and of animal fibers like hair and silk.
• The amino acid sequence of each of these proteins favors a particular kind of secondary structure, which confers on each protein a particular set of mechanical properties.

Factors Determining Secondary and Tertiary Structure

• The stability of the folded structure of a globular protein depends on the interplay of three factors:
  • Unfavorable conformational entropy change, which favors the unfolded state.
  • Favorable enthalpy contribution arising from intramolecular interactions.
  • Favorable entropy change arising from the burying of hydrophobic groups within the molecule.

Dynamics of Globular Protein Structure

• The folding of globular proteins from their denatured conformations is a remarkably rapid process, often complete in less than a second.
• Protein folding is not a completely random search through a vast conformational space, but rather takes place through a series of intermediate states.
• The “energy landscape” model suggests that the trajectory of protein folding is “downhill”—it proceeds with a decrease in free energy.
• Chaperones, such as the GroEL-GroES chaperonin, can help facilitate proper protein folding by preventing improper folding and aggregation.
• Protein misfolding is the basis for several diseases, including Alzheimer’s disease and Parkinson’s disease.