Protein Structure and Enzyme Function: A Study Guide

Protein Structure

Levels of Protein Structure

Proteins are complex biological macromolecules with multiple levels of structural organization. Each level contributes to the protein's final shape and function.

• Primary Structure: The linear sequence of amino acids in a polypeptide chain, held together by peptide bonds.

• Secondary Structure: Local folding of the polypeptide chain into structures such as alpha helices and beta sheets, stabilized by hydrogen bonds along the peptide backbone.

• Tertiary Structure: The overall three-dimensional shape of a single polypeptide chain, formed by interactions among the side chains (R groups) of amino acids.

• Quaternary Structure: The association of multiple polypeptide chains (subunits) to form a functional protein complex.

Example: Hemoglobin is a protein with quaternary structure, composed of four polypeptide subunits.

Protein Functions

Major Roles of Proteins in Cells

Proteins perform a wide variety of essential functions in living organisms:

• Cellular Transport: Proteins such as channels and co-transporters facilitate the movement of molecules across cell membranes.

• Immune Defense: Immunoglobulins (antibodies) and T cell receptors are proteins involved in recognizing and neutralizing pathogens.

• Storage: Proteins like ferritin and calmodulin store ions and other molecules for later use.

• Hormones: Some proteins, such as renin and leptin, act as hormones to regulate physiological processes.

• Gene Regulation: Transcription factors are proteins that control the expression of specific genes.

• Osmotic Regulation: Serum albumin helps maintain osmotic balance in the blood.

• Structural Support: Collagen provides structural integrity to connective tissues.

• Fuel: Some proteins can be broken down to provide energy.

• Enzymes: Proteins that catalyze biochemical reactions (approximately 75,000 different enzymes in humans).

Enzymes: Protein Catalysts

Definition and Function

Enzymes are proteins that act as biological catalysts. They speed up chemical reactions in the cell without being consumed in the process.

• Catalyst: A substance that increases the rate of a chemical reaction without undergoing permanent change.

• Specificity: Enzymes are highly specific for their substrates and the reactions they catalyze.

Enzyme Function – Basics

Enzymes work by binding to their specific substrate(s) at a region called the active site. This forms an enzyme-substrate complex, facilitating the conversion of substrates into products.

• Substrate: The molecule upon which an enzyme acts.

• Active Site: The region of the enzyme where the substrate binds and the reaction occurs.

General Reaction:

$E + S \rightarrow ES \rightarrow E + P$

• E: Enzyme

• S: Substrate

• ES: Enzyme-Substrate Complex

• P: Product

Example: The enzyme sucrase catalyzes the breakdown of sucrose into glucose and fructose.

Enzyme Specificity

Enzymes are reaction specific, meaning each enzyme typically catalyzes only one type of chemical reaction or acts on a specific substrate.

• Lock-and-Key Model: The substrate fits into the enzyme's active site like a key fits into a lock.

• Induced Fit Model: The enzyme changes shape slightly to accommodate the substrate for optimal catalysis.

Enzyme Kinetics

Key Parameters

Enzyme kinetics describes how the rate of enzyme-catalyzed reactions depends on various factors.

• Vmax: The maximum rate of the reaction when the enzyme is saturated with substrate.

• Km: The substrate concentration at which the reaction rate is half of Vmax. It is a measure of the enzyme's affinity for its substrate.

Michaelis-Menten Equation:

$V = \frac{V_{max}[S]}{K_m + [S]}$

• V: Reaction rate

• [S]: Substrate concentration

Enzyme Regulation

Enzyme activity can be regulated by various mechanisms, including the presence of inhibitors and changes in environmental conditions.

Enzyme Inhibitors

• Competitive Inhibitors: Molecules that resemble the substrate and compete for binding at the active site. They increase Km but do not affect Vmax.

• Noncompetitive Inhibitors: Molecules that bind to a site other than the active site, altering the enzyme's shape and function. They decrease Vmax but do not change Km.

Type of Inhibitor	Effect on Vmax	Effect on Km
Competitive	No change	Increases
Noncompetitive	Decreases	No change

Environmental Effects

• Temperature: Enzymes have an optimum temperature at which they function best. High temperatures can denature enzymes, causing loss of structure and function.

• pH: Each enzyme has an optimum pH. Deviations from this pH can reduce activity or denature the enzyme.

Example: Human enzymes typically have an optimum temperature around 37°C and specific pH optima (e.g., pepsin in the stomach works best at pH 2).

Protein Misfolding and Disease

Prions and Protein Misfolding

Proteins must fold into specific three-dimensional shapes to function properly. Misfolded proteins can aggregate and cause disease.

• Prions: Infectious proteins that cause other proteins to misfold, leading to neurodegenerative diseases.

• Diseases: Examples include mad cow disease (Bovine Spongiform Encephalopathy), scrapie, chronic wasting disease, and Creutzfeldt-Jakob disease.

• Mechanism: Misfolded prions induce normal proteins to adopt abnormal conformations, resulting in the formation of insoluble plaques in the brain.

Example: In prion diseases, the normal prion protein (PrP) converts to a disease-causing form, which is rich in beta sheets instead of alpha helices.

Additional info: Protein misfolding is also implicated in other diseases such as Alzheimer's and Parkinson's disease, where protein aggregates disrupt normal cellular function.