Proteins - Diversity and Diseases

Proteins - The Most Diverse Macromolecules

• Proteins are the most diverse macromolecules, exhibiting a vast array of sizes and shapes.
• Proteins have diverse functions, including catalysis (e.g., alcohol dehydrogenase), transport (e.g., hemoglobin), motor function (e.g., actin and myosin in muscle cells), structural roles (e.g., tendons, hair), immune function (e.g., antibodies), and hormonal/regulatory functions (e.g., hormones, transcription factors).
• Various proteins are listed in the images, including examples like cytochrome c, glucagon, insulin, and numerous enzymes.
• Proteins like hemoglobin, myoglobin, ferritin, and serum albumin are also key examples.

Protein Abnormalities and Diseases

• Sickle cell anemia is a disease caused by an abnormality in hemoglobin.
• Metabolic diseases can arise due to dysfunction in protein enzymes.
• Neurodegenerative diseases, like Alzheimer's, Parkinson's, and Huntington's, involve misfolded proteins such as amyloid beta peptide, phosphorylated tau, α-synuclein, and mutated huntingtin.

How Proteins Present Specific Functions

• Polypeptides fold into specific conformations determined by the amino acid sequence.
• This folding process is critical for proteins to exhibit their unique functions.

The Nobel Prize in Chemistry 2024

• The 2024 Nobel Prize in Chemistry was awarded to David Baker (computational protein design), Demis Hassabis, and John M. Jumper (protein structure prediction).

Topic Outline - Proteins

• Proteins are composed of 20 amino acids.
• Peptide bonds form polypeptides.
• Proteins have four structural levels: primary, secondary, tertiary, and quaternary.
• Hemoglobin structure is an example of protein structure.
• The text lists knowledge and comprehension skills associated with the structure of proteins (define, list, label, arrange, summarize, describe, discuss).
• The text explains application and analysis skills needed for protein studies (illustrate, interpret, compare, analyze).

Amino Acids - Learning Objectives

• Students should identify 20 common amino acids.
• They should describe physical and chemical properties of each amino acid.
• Students should understand the biological importance of amino acids and small peptides.

Amino Acids - Key Readings

• Specific biochemistry textbooks (Campbell, Farrell & McDougal, Lehninger Principles of Biochemistry, and Biochemistry, Berg, Tymoczko & Stryer) are recommended resources for studying amino acids, peptides, protein structures.
• The textbooks cover amino acid properties in detail.

Common Structural Features of α-amino Acids

• The α-carbon atom is attached to a carboxylate group, an amino group, and a side chain (R group).
• The R group dictates the unique identity of each amino acid.

3D-Shape (Stereochemistry) of Amino Acids

• Except for glycine, the α-carbon atom is a chiral center with four different groups attached.
• This results in two stereoisomers (L and D).
• Almost all amino acids in proteins are L-isomers.
• D-amino acids are found in some bacterial cell walls.

How to Distinguish L- and D-amino Acids

• The CORN rule is used to distinguish between L- and D-amino acids by looking at the spatial arrangement of the four substituent groups around the α-carbon atom.

Importance of Stereochemistry - The Thalidomide Tragedy

• Thalidomide, developed in the 1950s to treat morning sickness, had a serious side effect.
• A few years after the drug launch, thousands of infants were born with malformed limbs due to the different isomers having different effects.

Classification of the 20 Amino Acids

• Amino acids are classified based on the properties of their R groups.
• This classification includes hydrophobic (nonpolar), polar (neutral), and charged amino acids (positive or negative).

Polar vs. Non-polar Covalent Bonds

• Polar covalent bonds result from an unequal sharing of electrons between atoms with different electronegativities.
• Electronegativity values are presented for elements like C, S, N, and O.

A. Hydrophobic Amino Acids with Nonpolar R Groups

• Glycine is the simplest amino acid with a single hydrogen as its side chain.
• Alanine, valine, leucine, and isoleucine have aliphatic hydrocarbon chains as their side chains.
• Proline has a cyclic 5-membered aliphatic ring.
• Methionine has a sulfur atom in its side chain.
• Phenylalanine and tryptophan contain aromatic side chains.

B. Polar Amino Acids with Neutral R Groups

• Serine, threonine, and tyrosine have hydroxyl (-OH) groups attached to their side chains.
• Asparagine and glutamine have carboxylamide groups.
• These groups allow for hydrogen bonding.

Phosphorylation on Serine/Threonine/Tyrosine

• Signal transduction often involves covalent modifications like phosphorylation and dephosphorylation of proteins.
• ATP is the most common phosphoryl group donor.
• Serine, threonine, and tyrosine residues in proteins are commonly phosphorylated. This plays a crucial role in regulating protein function.

C. Cysteine and Disulfide Bridges

• Cysteine contains a sulfhydryl (-SH) group.
• Oxidation of two cysteine residues creates a disulfide bridge, which can stabilize protein structures.

Proper Folding of Insulin

• Insulin structures have intra- and inter-chain disulfide bonds crucial for the protein's proper folding and function.

Aromatic Amino Acids and Ultraviolet Absorption

• Aromatic amino acids absorb ultraviolet light. Absorption at 280nm in the ultraviolet region can be used to ascertain protein concentration.

C. Charged Amino Acids

• Aspartate and glutamate have carboxyl groups with pKa of 3.7 and 4 respectively. These groups become negatively charged at physiological pH.
• Lysine, arginine, and histidine are positively charged amino acids. Their side chains are amphipathic in nature. The pKa values for the amino, guanidino, and imidazole groups are 10.5, 12.5, and 6.0 respectively.

Acetylation of Histone Lysine Residues

• Histone proteins compact DNA, forming chromatin.
• Acetylation of lysine residues on histones opens up chromatin structure and enables access of RNA polymerase. This is a key process in regulating gene transcription. Deacetylation has the opposite effect, closing up the chromatin structure.

Rare Amino Acid: Selenocysteine

• Selenocysteine is the 21st amino acid.
• It is attached to a unique tRNA that recognizes the stop codon UGA.
• Selenocysteine is found in 25 human selenoproteins.