Proteins


  • Definition: Proteins are the most abundant and variable biological macromolecules.

    • Found in all parts of all cells in all organisms.

    • Among macromolecules, they show the greatest variety of:

    • Size

    • Structure

    • Function

  • Information Pathway: Proteins are the final part of the information pathway.

The Central Dogma of Biology

Simplified Version

  • Replication: DNA -> DNA (DNA Polymerase)

  • Transcription: DNA -> RNA (RNA Polymerase)

  • Translation: RNA -> Protein (Ribosome)

Slightly Less Simplified Version

  • DNA processes:

    • DNA Replication: DNA -> DNA (DNA Polymerase)

    • Reverse Transcription: RNA -> DNA (Reverse Transcriptase)

    • Transcription: DNA -> RNA (RNA Polymerase)

    • RNA Replication: RNA -> RNA (RNA Dependent RNA Polymerase)

    • Translation: RNA -> Protein (Ribosomes)

  • Different types of RNA:

    • (+) Sense RNA

    • (-) Sense RNA

Structure of Proteins

  • Description: Proteins are made as linear polymers (chains) of amino acids.

  • Building Blocks: Each organism uses the same ‘building blocks’: 20 amino acids from which all proteins are made.

  • Size Range: A single protein can contain from 50 to 30,000 amino acid residues.

  • Bonding: Each amino acid residue is joined to its neighbor by a covalent bond called a peptide bond (amide bond).

  • Hydrolysis: Proteins can be broken down or ‘hydrolyzed’ into their constituent amino acids.

Diversity of Protein Function

  • Enzymes: Catalysts for biochemical reactions.

  • Nutrient Proteins: Such as egg albumin and casein (milk).

  • Transport Proteins: Carry materials within organisms.

  • Regulatory Proteins: Important for metabolism and cell function (e.g., hormones, receptors).

  • Signaling Proteins: Involved in cell-cell communication.

  • Structural Proteins: Include keratin (hair, feathers), collagen, and actin.

  • Movement Proteins: Examples include myosin and flagella.

  • Information Decoding: Functions in transcription and translation.

  • Antibodies: Provide immune defense.

Diversity of Protein Size, Shape & Structure

  • Examples of various proteins:

    • Phosphocarrier protein HPr

    • Enzymes such as lysozyme and catalase

    • Transport proteins like myoglobin and hemoglobin

    • Structural proteins such as collagen and tubulin

Introduction to Amino Acids

  • Common Structure: All amino acids share a common structure consisting of:

    1. An a-carbon bonded to:

      • A carboxylic acid (COOH)

      • An amine (NH2)

      • A hydrogen atom (H)

      • A variable side chain (R group)

  • Type: The 20 natural amino acids are termed a-amino acids.

Amino Acids' Variability

  • Amino acids differ only in their R group (side chain).

  • Each amino acid is assigned three identifiers:

    1. Name: Non-systematic names (e.g., cysteine).

    2. Three-letter code: (e.g., cys, lys, asp)

    3. Single-letter code: (e.g., C, K, E)

  • Importance: Knowledge of the names, abbreviations, chemical structure, and properties of the 20 natural amino acids is essential for this unit and others to follow.

Historical Context of Amino Acid Names

  • Non-systematic names often derived from substances they were first isolated from:

    • Asparagine: Found in asparagus.

    • Glutamic acid: Found in wheat gluten.

    • Tyrosine: Isolated from cheese (Greek tyros).

    • Serine: Isolated from silk (Latin sericum).

Key Features of Amino Acids

Charge

  • At physiological pH (pH 7), all amino acids carry distinct charges:

    • Negative charge on carboxyl group (COO-)

    • Positive charge on amine group (NH3+)

    • Some side chains can also carry additional charges.

Chirality

  • All amino acids (except glycine) have four different groups attached to the a-carbon, designating it as a chiral center.

  • Two configurations (spatial arrangements) are possible:

    • Chirality: A molecule is chiral if it has no plane of symmetry and non-superimposable mirror images.

    • A chiral carbon atom with four different groups results in optical isomers (enantiomers).

  • Racemic Mixture: A 50:50 mixture of enantiomers that does not affect plane polarized light.

    • Enantiomers rotate polarized light in opposite directions.

Super-Imposability

  • Two objects are super-imposable if they can perfectly overlap when placed in the same location.

Examples in Chirality

  • Thalidomide: Consists of R and S enantiomers:

    • R-Thalidomide: Sleep-inducing effect.

    • S-Thalidomide: Teratogenic effect (causing birth defects).

3D Representation of Amino Acids

  • Modeling: 3D ball & stick model of serine highlights structural components:

    • a-Carboxylate group

    • a-Amino group

    • a-Carbon (with side chain for serine: -CH2OH).

Fischer Projections and Enantiomers

  • Fischer projections of L and D-alanine show the arrangement of carbon atoms:

    • Drawn with the carbon chain vertically and the most oxidized carbon (aCOOH) at the top.

  • Key Concept: Amino acids in proteins exist exclusively in the L-stereoisomer form.

  • Natural sugars (e.g., glyceraldehyde) exist exclusively as the D-stereoisomer.

Numbering Systems for Carbon Atoms in Amino Acids

  • Two Systems Used:

    • a, b, g, d (from the a-amino and carboxyl groups).

Classification of Amino Acids

  • Can be classified according to various criteria:

    • By chemical nature of side chains:

    1. Nonpolar (hydrophobic)

    2. Polar neutral (hydrophilic)

    3. Polar positively charged (hydrophilic)

    4. Polar negatively charged (hydrophilic)

Bond Polarity and Electronegativity

  • Bond Polarity: Based on the electronegativity difference between atoms in the bond.

  • Electronegativity Values:

    • Carbon: 2.5

    • Hydrogen: 2.2

    • Nitrogen: 3.1

    • Oxygen: 3.4

  • Examples:

    • C-C bonds (electronegativity difference = 0) are nonpolar.

    • O-H bonds (electronegativity difference = 1.2) are polar.

Nonpolar (Hydrophobic) R Groups

  • Examples:

    • Glycine (Gly)

    • Alanine (Ala)

    • Valine (Val)

    • Leucine (Leu)

    • Isoleucine (Ile)

    • Phenylalanine (Phe)

    • Proline (Pro)

    • Tryptophan (Trp)

    • Methionine (Met)

Polar but Uncharged R Groups

  • Common polar functional groups include:

    • -C-OH

    • -N-H

    • -C=O

    • -SH

    • -CONH2

  • Characteristics:

    • Polar due to electronegativity difference.

    • Uncharged as they do not donate or accept protons.

    • Interact with water primarily through hydrogen bonding.

Polar, Uncharged Hydrophilic R Groups

  • Examples:

    • Serine (Ser)

    • Threonine (Thr)

    • Tyrosine (Tyr)

    • Cysteine (Cys)

    • Asparagine (Asn)

    • Glutamine (Gln)

Positively Charged R Groups (Basic Side Chains, Hydrophilic)

  • Examples:

    • Lysine (Lys)

    • Arginine (Arg)

    • Histidine (His)

Negatively Charged R Groups (Acidic Side Chains, Hydrophilic)

  • Examples:

    • Aspartate (Asp)

    • Glutamate (Glu)

Hydropathy Index

  • Hydropathy Scale for Amino Acid Residues:

    • Shows the free-energy change for transfer in kJ mol¯1.

    • Amino acids ordered from highly hydrophobic to highly hydrophilic:

    • Isoleucine: +3.1

    • Phenylalanine: +2.5

    • Valine: +2.3

    • Leucine: +2.2

    • Methionine: +1.1

    • (Continuing to less hydrophobic values down to negatively charged amino acids.)

Summary of Amino Acid Classifications

  • Main Groupings of Amino Acid Side Chains:

    • Hydrophobic: Glycine, Alanine, Valine, Isoleucine, Leucine, Phenylalanine, Proline, Tryptophan, Methionine.

    • Polar but Uncharged: Serine, Threonine, Tyrosine, Cysteine, Asparagine, Glutamine.

    • Positively Charged (Basic): Lysine, Arginine, Histidine.

    • Negatively Charged (Acidic): Aspartate, Glutamate.

  • Amino Acid Structure Recap:

    • Chiral α carbon bonded to four different groups, including Amine (positively charged), Carboxylic acid (negatively charged), Hydrogen, and R groups (20 different).