lecture 3 summary

Proteins Overview

• Definition: Proteins are long chains of amino acids, typically containing 250 to 500 amino acids, though some can exceed 10,000.

• Bonding: Amino acids are connected by peptide bonds, which are single covalent bonds that impart flexibility and polarity.

• Proteinogenic Amino Acids: There are 20 central amino acids in proteins, with additional rare amino acids like hydroxyproline and selenocysteine.

Amino Acids

• Structure: Amino acids consist of an amine group, a carboxyl group, and a central carbon with one or two hydrogens.

• Isomerism: Amino acids exist in D-stereo and L-stereo forms, with the L-isomers being the standard in proteins.

• Rare Amino Acids: Some amino acids are added post-translationally, expanding the array of protein structure.

Basic Protein Structure

• Backbone Structure: All proteins share a similar backbone structure: H2N—C—COOH, differing only in their R-groups (side chains).

• Side Chain Properties: The unique properties of side chains influence the overall characteristics of the protein.

Determining 3D Structure

• Factors Influencing Structure: The 3D structure emerges from interactions between side chains, peptide bonds, and solvent (water).

• Dynamic Conformation: Proteins continuously fold and unfold; the final state corresponds to the lowest energy configuration.

Types of Interactions

• Electrostatic Forces: Include hydrogen bonds, van der Waals attractions, and ionic bonds (primarily within the interior).

• Hydrophobic Interactions: Nonpolar side chains tend to cluster together, minimizing interaction with water.

• Covalent Disulfide Bonds: Occur between cysteine residues, adding stability to the protein structure.

Levels of Protein Structure

• Primary Structure: Linear sequence of amino acids connected by peptide bonds.

• Secondary Structure: Formed by hydrogen bonds between peptide bonds; commonly includes α-helices and β-sheets.

• Tertiary Structure: Overall 3D shape from folding, driven largely by non-covalent interactions, with possible ionic and covalent bonds.

• Quaternary Structure: Complexes of multiple polypeptide chains forming a functional protein, relying on non-covalent interactions.

Protein Domains

• Definition of Domains: Distinct functional or structural units within proteins, such as DNA-binding or ATP-binding domains.

• Diversity: Many proteins possess similar domains that serve specific functions.

Potential Protein Variability

• Amino Acid Combinations: With 20 amino acids, a 300-residue protein can have 10^390 different arrangements.

• Natural Selection: Only a fraction of these combinations have biological significance; selected proteins must be stable and beneficial.

Protein Function

• Importance of Shape: The surface shape and chemistry of proteins are crucial for their interactions with other biomolecules.

• Binding: Proteins interact with other molecules (ligands) through a set binding site, often spatially located in a cavity or on surfaces.

Binding and Conformational Change

• Effect of Binding: The binding of molecules can alter the chemical environment of proteins, leading to shape changes known as conformational shifts.

• Implications: Changes can create or eliminate binding sites and modify functions.

Enzymatic Function

• Role of Enzymes: Proteins that function as biological catalysts, facilitating and accelerating biochemical reactions.

• Reaction Mechanism: Enzymes bind substrates and convert them to products, following the reaction sequence: E + S → ES → EP → E + P.

Enzyme Catalysis

• Enhancement of Reactions: Enzymes position substrates correctly, alter electron distributions, and stabilize transition states for faster reactions.

Acid-Base Catalysis

• Mechanism: Acids and bases facilitate bond hydrolysis; for example, an acid can donate H+, making atoms more reactive.

• Dual Role: Enzymes use both acidic and basic side chains to interact with substrates effectively.

Lysozyme Case Study

• Function: Lysozyme hydrolyzes glycosidic bonds in bacterial cell walls.

• Mechanics: The enzyme binds to its substrate, distorting sugar conformations and promoting reaction completion.

Non-Protein Components

• Cofactors and Coenzymes: Many proteins require additional small molecules or metal ions, which support their catalytic functions.

Protein Complexes and Tunnel Structures

• Molecular Tunnels: Pathways that connect active sites, isolating reactive intermediates and facilitating efficient reactions.

Regulation of Protein Function

• Control Mechanisms: Protein function is regulated through synthesis rates, degradation, and direct control of activity.

• Conformational Changes: Alterations in protein shape due to ligand binding or post-translational modification lead to changes in activity.

Feedback Regulation in Enzymes

• Mechanisms of Feedback: End products of metabolic pathways often regulate their own synthesis, maintaining homeostasis through negative feedback.

• Positive Feedback: Substrate accumulation can enhance enzyme activity, exemplifying a stimulatory regulatory mechanism.

Phosphorylation and GTP Regulation

• Phosphorylation: The addition of phosphate groups affects protein conformation, potentially activating or inhibiting activity.

• GTPases: GTP binding activates proteins, with hydrolysis to GDP leading to deactivation, illustrating a cyclic regulatory mechanism.

Protein Functions Beyond Catalysis

• Transport and Synthetases: Proteins may serve as pumps to move molecules across membranes or synthesize ATP using electrochemical gradients.

• Motor Proteins: Essential for muscle contraction and intracellular transport, indicative of diverse protein roles in cellular function.