Protein Midterm

Non-Polar Amino Acids

• Have uncharged, often bulky side chains

• Hydrophobic

Polar Amino Acids

• Have side chains with dipoles

• Can form hydrogen bonds in water: hydrophilic

Charged Amino Acids

Have side chains with ionic charges at physiological pH

Amino group, carboxylic acid group, alpha carbon, and side chain (R group).

What are the four parts of a typical amino acid?

A dehydration (condensation) reaction.

What reaction forms a peptide bond?

Water

Peptide bond formation releases ______.

Double-bond

Peptide bond resonance produces partial ______ character.

N

Phi (φ) describes rotation around the ______–Cα bond.

C (carbonyl carbon)

Psi (ψ) describes rotation around the Cα–______ bond.

Hydrogen

Glycine's R group is ______.

0.4–4.0

Van der Waals interactions are approximately – kJ/mol.

12–30

Hydrogen bonds are approximately – kJ/mol.

3.6

An alpha helix has ______ residues per turn.

5.4

An alpha helix has a pitch of ______ Å

Protein

Secondary structures begin forming during ______ synthesis.

Opposite

Antiparallel beta strands run in ______ directions.

Same

Parallel beta strands run in the ______ direction.

Entropy

The hydrophobic effect helps maximize ______ by reducing nonpolar surface exposure to water.

Alpha carbon (Cα)

The central carbon attached to the amino group, carboxyl group, hydrogen, and R group

Amino Group

The nitrogen-containing group of an amino acid.

Carboxylic Acid Group

The acidic functional group of an amino acid.

Side chain (R group)

The variable group attached to the alpha carbon that gives each amino acid its unique properties.

Peptide Bond

A covalent bond linking amino acids in a protein's backbone.

Peptide Bond Resonance

The sharing of electrons across the peptide bond, giving it partial double-bond character.

Peptide Bond Flexibility

Limited flexibility caused by resonance; the peptide bond is not completely rigid.

Trans Peptide Bond

A peptide bond arrangement in which adjacent alpha carbons lie on opposite sides of the peptide bond.

Cis Peptide Bond

A peptide bond arrangement in which adjacent alpha carbons lie on the same side of the peptide bond.

Proline

is more likely than most amino acids to occur in the cis configuration.

Phi (φ) Angle

The torsion angle describing rotation around the N–Cα bond.

Psi (ψ) Angle

The torsion angle describing rotation around the Cα–C bond.

Steric Hindrance

Interference that occurs when atoms are too close together, restricting possible molecular conformations.

Ramachandran Plot

A plot showing the allowed combinations of phi (φ) and psi (ψ) angles in a protein backbone.

Proline

An amino acid with a rigid, cyclic side chain that restricts backbone flexibility.

Glycine

An amino acid with hydrogen as its R group, allowing greater backbone flexibility.

Work

Force multiplied by distance

Secondary Structure

Local, recurring arrangements of a protein backbone, including alpha helices and beta sheets.

Primary Structure

The amino acid sequence of a protein.

Secondary Structure Formation

Begins during protein synthesis, before the protein is released from the ribosome.

Hydrophobic Effect

The tendency of nonpolar molecules or groups to associate in water, minimizing their exposure to the polar solvent.

Water Cages

Ordered arrangements of water molecules around nonpolar molecules that restrict water movement.

Beta Turn

A short region of a polypeptide chain that reverses its direction.

Beta Hairpin

A structure in which a chain reverses direction, allowing two beta strands to lie alongside one another.

Beta Sheet

A secondary structure formed by neighboring beta strands stabilized by hydrogen bonds

Amphipathic Structure

A structure containing both hydrophilic (polar) and hydrophobic (nonpolar) regions.

Tertiary Structure

The overall 3D shape of a protein.

Cis

Only about 0.05% of peptide bonds are _____

Gibbs free energy (ΔG)

The energy change that helps determine whether folding is favourable.

Negative

Protein folding requires an overall ______ ΔG.

ΔH

The equation for Gibbs free energy is ΔG = ______ − TΔS.

Conformational Entropy

A measure of disorder or the number of different physical shapes (conformations) a molecule can adopt.

Lower

A folded protein has ______ conformational entropy than an unfolded protein.

Collapse

The early clustering of hydrophobic regions is called hydrophobic ______.

Hydration Shell

The layer of water around a protein

Folding Intermediates

Partially folded structures formed before the final native state.

Native State

The properly folded, functional form of a protein.

Levinthal's Paradox

• Unbiased, random search through all physical configurations.

• Proteins cannot fold by randomly testing every possible conformation because it would take too long.

Protein Aggregation

The clumping together of proteins.

Molecular Chaperones

Proteins that help other proteins fold and reduce inappropriate aggregation.

Intrinsically unstructured proteins (IUPs)

Proteins that lack a stable folded structure in solution.

Ligand-Induced Folding

Folding that occurs when an unstructured protein interacts with a binding partner.

99

In a 100-amino-acid protein, there are ______ peptide bonds.

Collapse

The main driving force for initiating folding is hydrophobic ______.

Surface

Internal amino acid residues generally influence tertiary structure more than ______ residues.

Hierarchical Folding

Small protein structures form first and combine into larger structures.

Classical / linear pathway model

Protein folding occurs through a step-by-step sequence of well-defined intermediate states.

Landscape theory (energy funnel model)

Proteins fold across an energy landscape, progressing from many possible conformations toward the lower-free-energy native state.

Hydrophobic Collapse Model

• Accepted as an important folding mechanism, but not universal.

• Hydrophobic amino acids cluster away from water, initiating folding and forming a compact structure

Nucleation-Condensation Model

Accepted for some proteins, but not universal. Local secondary structures and long-range tertiary contacts form together around a small structural nucleus.

Co-Translational Folding

Accepted. Proteins can begin folding while their amino acid chains are still being synthesized by the ribosome.

Two-state folding mechanism

Accepted for some proteins, but not universal. A protein transitions directly between unfolded and native states without stable intermediate structures.

Cofactor

A non-protein component that helps a protein perform a chemical function.

Coordinate covalent bond

A bond in which both shared electrons are donated by one atom.

Denaturation

The disruption of a protein's native structure, often causing loss of function.

Marginal protein stability

Native protein structures are only slightly more stable than their denatured forms.

Denaturing Agents

Substances or conditions that disrupt protein structure, including detergents, metals, soluble organic compounds, colloids, nanoparticles, crowding, and hydrostatic pressure.

Denaturing external environments

External conditions that can disrupt protein structure, including extreme temperatures, salinity, pH, contaminants, and pressure.

Denaturing internal environments

conditions such as temperature stress, oxidative stress, ATP shortage, dehydration, infections, macrophage activity, and prions.

Oxidative stress

Damage associated with reactive oxidative species; it can occur during hypothermia or hyperthermia.

Post-translational modifications

Chemical modifications made to amino acids after they have been incorporated into a protein.

Stabilizing amino acid substitutions

Amino acid changes that introduce stabilizing interactions, such as hydrogen-bond donors or disulfide bonds.

Antifreeze proteins

Proteins that bind to ice and control ice crystal formation.

Ice-binding face

The surface of an antifreeze protein that binds to ice; hydrophobic.

Kelvin effect

The effect associated with curvature influencing ice growth; antifreeze proteins force curvature onto ice surfaces to inhibit growth.

Kosmotropic salts

Stabilizing salts that enhance water–water interactions and help stabilize weak forces in native proteins.

Chaotropic salts

Denaturing salts that weaken water–water hydrogen bonding and can destabilize protein structure.

Protein precipitation

The formation of an insoluble protein aggregate or solid from solution.

Detergents

Agents that can disrupt protein structure by interacting with hydrophobic regions and competing with normal interactions.

SDS

A detergent used in denaturing electrophoresis to disrupt native protein structure.

Urea

A chaotropic agent that promotes protein unfolding.

Counteracting solutes

Stabilizing substances that oppose the effects of denaturing agents.