Proteins - The Most Diverse Macromolecules

Proteins - The Most Diverse Macromolecules

• Proteins are the most diverse macromolecules, exhibiting a vast array of sizes and shapes.
• Countless proteins are listed in the image, including: Cytochrome c, Glucagon, Insulin, ATP Synthase, Aquaporin, Potassium Channel, Mechanosensitive Channel, Gramicidin, Porin, Hemoglobin, Myoglobin, Ferritin, Serum Albumin, Phosphoglucose Isomerase, Aldolase, Triosephosphate Isomerase, Phosphofructokinase, Enolase, Pyruvate Kinase, Cytochrome b-c1 Complex, Cytochrome c Oxidase, Phosphoglycerate Kinase, Glyceraldehyde-3-phosphate Dehydrogenase, Tryptophan Synthase, Phosphoglycerate Mutase, Dihydrofolate Reductase, Human Growth Hormone, Interferon, Deoxyribonuclease, Trypsin, Lysozyme, Rhodopsin, Ribonuclease, Pepsin, Amylase, Phospholipase, Antibody, Alcohol Dehydrogenase, Thymidylate Synthase, Glutamine Synthetase, Cyclooxygenase, Aspartate Carbamoyltransferase, Ribulose Bisphosphate Carboxylase/Oxygenase, Nitrogenase, Photosynthetic Reaction Center, Light-Harvesting Complex, Valyl-tRNA Synthetase, Threonyl-tRNA Synthetase, Isoleucyl-tRNA Synthetase, Phenylalanyl-tRNA Synthetase, Glutaminyl-tRNA Synthetase, Elongation Factor Tu, Aspartyl-RNA Synthetase, Elongation Factor G, Elongation Factor Tu and Ts, Ribosome, Proline cis/trans Isomerase, Prefoldin, Transfer RNA, Chaperonin GroEL/ES

Protein Functions

• Proteins perform various essential functions, including:
  • Catalysis: Examples include alcohol dehydrogenase
  • Transport: Examples include hemoglobin
  • Motor: Examples include actin and myosin in muscle cells, tendons, and hair
  • Defense: Examples include antibodies
  • Signaling: Examples include hormones and transcription factors

Protein Abnormalities and Diseases

• Sickle cell anemia: An abnormality in hemoglobin.
• Metabolic diseases: Dysfunction of protein enzymes.
• Neurodegenerative diseases: Misfolded proteins (e.g., Alzheimer's, Parkinson's, Huntington's diseases).Specific implicated proteins are highlighted (Amyloid-β peptide, tau, α-synuclein, mutated huntingtin protein).

Protein Structure and Function

• Polypeptides fold into specific shapes depending on their amino acid sequences.

The Nobel Prize in Chemistry 2024

• Prizes were divided concerning computational protein design and protein structure prediction.

Protein Composition and Structure

• Amino acids: The building blocks of proteins (20 common amino acids)
• Peptide bonds: Form polypeptides.
• Four levels of protein structure: Primary, secondary, tertiary, and quaternary structures.

Amino Acids

• Learning Objectives:
  • Identify 20 common amino acids and their physical and chemical properties.
  • Understand the biological importance of amino acids and small peptides.
• The 20 common amino acids are classified by chemical characteristics of their R groups (hydrophobic, polar, charged)

Common Structural Features of Amino Acids

• All α-amino acids have an α-carbon atom bonded to a carboxylate group, an amino group, and a side chain (R group).
• The R group dictates the unique identity and properties of each amino acid.

3D Shape (Stereochemistry) of Amino Acids

• All amino acids (except glycine) have a chiral carbon (α-carbon).
• Most naturally occurring amino acids in proteins are L-isomers.
• D-amino acids are found in bacterial cell walls

Distinguishing L- and D-amino acids

• CORN rule: An easy method to determine whether specific amino acid is L or D form.

Importance of Stereochemistry

• The thalidomide tragedy: Demonstrates the critical importance of stereochemistry in drug design and safety. Separation of isomers is not sufficient to preclude issues relating to enantiomers.

Classification of the 20 Amino Acids

• Classification based on the chemical characteristics of their R groups.
• Hydrophobic amino acids with nonpolar R groups
• Polar amino acids with neutral R groups
• Charged amino acids with R groups that have a positive or negative charge at physiological pH

Polar vs. Non-polar Covalent Bonds

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

Aromatic Amino Acids

• Aromatic amino acids absorb ultraviolet light.
• Measurement of absorbance at 280 nm can be used to measure protein concentration.

Charged Amino Acids

• Negatively charged amino acids: Carboxylate groups of aspartate and glutamate have pKas of 3.7 and 4.0, respectively. They are ionized (negatively charged) at physiological pH.
• Positively charged amino acids: pKa values for lysine, arginine, and histidine side chains (~10.5, ~12.5, ~6.0). Lysine and arginine side chains are amphipathic.

Acetylation of Histone Lysine Residues

• DNA in chromatin is tightly associated with histone proteins via the packaging of DNA into nucleosomes.
• Acetylation of histone lysine residues opens up chromatin structure, allowing RNA polymerase access for transcription process. Deacetylation closes chromatin, hindering access.

Rare Amino Acid: Selenocysteine

• Selenocysteine, the 21st amino acid.
• Attached to a unique tRNA that recognizes the stop codon UGA.
• Found in 25 human selenoproteins.

Explore the fascinating world of proteins, the most diverse macromolecules in biology. This quiz challenges your knowledge about various proteins, their functions, and their significance in biological processes. Test your understanding of key proteins like Hemoglobin, Insulin, and many others listed in the quiz.