Biochemistry: pKa Values and Dielectric Constants

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Questions and Answers

What happens to the pKa value of an amino acid when it is situated within a protein structure?

It remains unchanged regardless of the environment.

It is solely determined by the solvent used.

It decreases only if the residue is hydrophobic.

It can shift due to local interactions influencing ionization. (correct)

What specifically favors the protonation of Glu172 in xylanase?

The absence of water molecules in the vicinity.

The presence of nearby nonpolar residues.

An increase in temperature during the reaction.

Electrostatic repulsion between charged adjacent glutamate residues. (correct)

How does the dielectric constant affect electrostatic interactions in different media?

Lower dielectric constants enhance electrostatic interactions.

Higher dielectric constants weaken electrostatic interactions. (correct)

Dielectric constants are only relevant in vacuum conditions.

The dielectric constant has no effect on electrostatic interactions.

Why does water have a high dielectric constant compared to organic solvents?

Water possesses a strong dipole moment and is very mobile. Signup and view all the answers

What role do mobile dipoles play in the context of charge-charge interactions?

They reorient to counteract local electrostatic fields. Signup and view all the answers

What is the dielectric constant of a typical protein core?

Around 10 Signup and view all the answers

What is a salt bridge in protein interactions?

Interaction between a negatively charged residue and a positively charged group Signup and view all the answers

How do charged residues contribute to protein solubilization?

They enhance binding with water and ions Signup and view all the answers

What is the main consequence of protein folding in terms of entropy?

Reduction in conformational entropy Signup and view all the answers

Which amino acids can engage in cation-pi interactions?

Arginine and Lysine Signup and view all the answers

What happens to mobile dissolved ions in the presence of proteins?

They compete with proteins for charge interactions Signup and view all the answers

Why are salt bridges considered temperature independent?

Their stability is unaffected by temperature changes Signup and view all the answers

What is the typical interaction strength of cation-pi interactions?

12 kJ/mol Signup and view all the answers

What contributes to the entropic costs when proteins fold?

Decreased number of available conformations Signup and view all the answers

Why are buried charged residues energetically costly?

They require stabilization through multiple H-bonds Signup and view all the answers

What drives the behavior of liquid water?

Strong, directional hydrogen bonds Signup and view all the answers

How do non-polar solutes affect water molecules?

They disrupt the network of hydrogen bonds Signup and view all the answers

What is the term used to describe the relative preferences for aqueous and nonpolar environments?

Hydropathy Signup and view all the answers

What does a negative free energy of transfer (GTr) indicate?

The molecule prefers a non-aqueous environment Signup and view all the answers

What primarily results in the unfavorable transfer of a nonpolar molecule from a nonpolar liquid to water?

Unfavorable change in entropy Signup and view all the answers

What happens to the hydrophobic effect as temperature increases?

It becomes less pronounced Signup and view all the answers

How is the partition coefficient (KD) calculated?

By dividing the concentration of the nonpolar solvent by the concentration of water Signup and view all the answers

What is the approximate value of the hydrophobic effect at 25˚C for buried non-polar surface?

0.1 kJ/mol/Å² Signup and view all the answers

Which component is NOT a characteristic of hydropathy?

An actual measurement of hydrophobicity Signup and view all the answers

What effect do polar groups have on the free energy of transfer for amino acid residues?

They dominate the free energy of transfer for most residues Signup and view all the answers

What is unique about glycine compared to other amino acids?

It is achiral. Signup and view all the answers

What structural feature of proline limits its rotation around the Cα-N bond?

An imine ring. Signup and view all the answers

Which of the following amino acids is chemically inert and non-polar?

Methionine Signup and view all the answers

Which aromatic amino acid possesses a hydroxyl group capable of forming hydrogen bonds?

Tyrosine Signup and view all the answers

What is a key feature of tryptophan's side chain?

It includes an indole ring. Signup and view all the answers

Which of the following amino acids is less likely to be buried within a protein?

Ala Signup and view all the answers

What characteristic allows methionine to be flexible among non-polar amino acids?

Two methyl groups next to the sulfur. Signup and view all the answers

What is the typical orientation of hydrophobic residues like Ala, Val, Leu, and Ile in proteins?

Prefer to be buried in the protein's interior. Signup and view all the answers

What is the approximate contribution of the hydrophobic effect from a side chain with a surface area of approximately 140 Å² when completely buried?

14 kJ/mol Signup and view all the answers

What distance is typical for a hydrogen bond interaction?

2.4-3.4 Å Signup and view all the answers

What characterizes the central region of membrane-embedded proteins?

It consists mostly of hydrophobic residues. Signup and view all the answers

How do bound lipid molecules interact with membrane proteins?

They bind in the grooves between helices. Signup and view all the answers

Which of the following amino acids is considered non-polar?

Leucine Signup and view all the answers

What role do non-polar amino acids predominantly serve in proteins?

They package together in the protein's interior. Signup and view all the answers

Which interaction typically occurs at a distance of approximately 4 Å?

Cation-pi interaction Signup and view all the answers

What is true about peptide bonds in proteins?

They create secondary structure through hydrogen bonding. Signup and view all the answers

What is the approximate width of the central region of the lipid bilayer occupied by hydrophobic tails?

~30 Å Signup and view all the answers

Which statement correctly describes the role of surface area in the burial of non-polar amino acids?

The greater the surface area, the stronger the preference for burial. Signup and view all the answers

Study Notes

The effect of structure on pKa values

The pKa value of a residue, which reflects its propensity to be protonated or deprotonated, can differ significantly within a protein compared to its solution value.
The pKa shift arises from local interactions within the folded protein, which can favor a specific residue to be either neutral or charged, altering the energetics of protonation.

Mobile Dipoles and Dielectric Constant

The dielectric constant of a medium influences the strength of electrostatic interactions, with higher dielectric constants attenuating these interactions.
Water has a high dielectric constant due to its strong dipole moment and mobility, while non-polar solvents have low dielectric constants due to their weaker dipoles.
The dielectric constant within a protein varies depending on location, with the protein interior having a lower dielectric constant than the surface.

Charge Interactions in Proteins

The protein surface is typically dominated by charged residues, which interact with the solvent and dissolved ions.
These charge-charge interactions are weakened by competition from dissolved ions.
Charged residues contribute to protein solubility, but often do not form stable pairs.
The low dielectric constant of protein interiors disfavors burial of charged residues, requiring stabilization by multiple hydrogen bonds.

Salt Bridges

A salt bridge is a stabilizing interaction between oppositely charged residues, driven by electrostatic and hydrogen bonding forces.
They contribute significantly to the stabilization of proteins, especially in less dielectric environments.
Due to their temperature independence, salt bridges are crucial for stabilizing thermophilic proteins, which function at high temperatures.

Cation-Pi Interactions and Pi-Pi Stacking

Aromatic residues, due to their delocalized pi electrons, can form favorable interactions with positive charges (cation-pi) and with each other(pi-pi stacking).
This interaction strength is around 12 kJ/mol.

Entropic Contributions to Protein Energetics

Entropy, reflecting the number of available states for a system, influences protein folding.
Changes in protein conformation involve changes in the entropy of the protein itself (conformational entropy) and the entropy of surrounding water (hydrophobic effect).

Folding a Protein Entails Loss of Conformational Entropy

Protein chains are highly flexible and sample a vast number of conformations in solution.
This conformational entropy is significantly reduced upon folding into a defined structure, representing an entropic cost.

Conformational Entropy and Amino Acid Architecture

Hydrophobic amino acids, with fewer rotatable bonds, minimize the entropic cost of burial.
Many hydrophilic amino acids, with greater flexibility, tend to be surface exposed.

Liquid Water Structure

The structure of liquid water is based on extensive hydrogen bonding, involving a continuous dynamic network.

The Hydrophobic Effect

Non-polar solutes disrupt the water network, forcing rearrangement to maintain hydrogen bond integrity, creating cage-like structures.
These cages restrict water molecule mobility, resulting in an entropic penalty for dissolving non-polar molecules.
However, association of non-polar solutes releases some "caged" water molecules, leading to a net entropic gain and driving interactions between them.

Measuring Hydropathy

Hydropathy is an empirical measure of the preference of a molecule for an aqueous or nonpolar environment.
It can be measured as a partition coefficient between water and a nonpolar solvent, with a negative free energy of transfer indicating a preference for a non-aqueous environment.

Hydrophobic Interactions of Amino Acid Residues

The free energy of transfer for non-polar amino acids is proportional to their surface area.
At 25°C, the hydrophobic interaction contributes approximately 0.1 kJ/mol/Å2 buried non-polar surface area.

The Lipid Bilayer

The lipid bilayer provides a non-aqueous environment with a hydrophobic core.
Membrane proteins embedded in the bilayer typically have hydrophobic regions spanning this central core.

Membrane Embedded Proteins

The region of membrane proteins spanning the bilayer is dominated by hydrophobic residues. Aromatic residues with partial hydrophilic character are concentrated at the interface with the aqueous environment.

Bound Lipid Molecules

Membrane protein structures often show bound lipid molecules, associated with the protein even after detergent extraction.
These lipids typically bind in grooves between helices, forming a well-ordered layer analogous to the water layer surrounding soluble proteins.

Amino Acid Diversity

The chemical diversity of proteins arises from the polymerization of 20 different amino acids, with additional diversity created by covalent modifications after translation.

Interactions Within the Backbone: Peptide Bonds

Peptide bonds form amide groups, which participate in hydrogen bonding, driving the formation of secondary structure.

Non-Polar Amino Acids

Gly, Ala, Val, Leu, Ile, Met, Pro, Cys, and Phe are non-polar and tend to be buried within the protein interior.
Their preference for burial is proportionate to their surface area.
They can also be found on the surface, particularly in ligand binding sites.

Glycine

Glycine is the smallest amino acid, flexible and can be both buried or surface exposed.
Its achiral nature allows greater conformational flexibility than other amino acids.

Proline

Proline's rigid structure, containing an imine ring, limits its rotational flexibility and prohibits it from acting as a hydrogen bond donor.

Smaller Hydrophobic Amino Acids

Ala, Val, Leu, and Ile are small hydrophobic residues, preferring burial with varying degrees.
Their differences in volume and shape contribute to packing within the protein interior.
Methionine, with a sulfur atom, is non-polar and flexible.

Aromatic Amino Acids: Phenylalanine, Tyrosine, and Tryptophan

These amino acids have aromatic rings, contributing to hydrophobicity.
Tyrosine's hydroxyl group can form hydrogen bonds, while Tryptophan's indole ring contains a nitrogen capable of hydrogen bonding.

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Description

Explore the complex relationship between protein structure and pKa values, as well as the dielectric constant's impact on charge interactions. This quiz covers how local interactions influence protonation states and how the dielectric environment varies within proteins. Test your knowledge of these fundamental concepts in biochemistry.