Introduction+to+Proteins+I


 * 21 August 2006**
 * Introduction to Proteins I**
 * Dr. Kandice Williams, Ph.D.**

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=**Covalent Bonds**=


 * Strongest biochemical bond
 * Example: benzene resonance structure
 * Peptide bonds take 732 kJ/mol to dissociate
 * Formed by sharing a pair of electrons between adjacent atoms
 * Chemical reactions requiring the most energy break and form covalent bonds

=**Electrostatic Interactions**=


 * Depend on electrical charge of atoms
 * Atoms with single opposite charges in water take ~6 kJ/mol to dissociate
 * Dielectric constant of water is very high, D = 80

=**Hydrogen Bonds**=


 * Interactions are also weak electrostatic interactions
 * Longer than covalent bonds
 * Energy of dissociation = ~4-13 kJ.mol
 * Hydrogen atom is shared between two electron negative atoms (nitrogen or oxygen)
 * One is the hydrogen bond donor (+), the other is the hydrogen bond acceptor (-)

=**van der Waal Interactions**=


 * Important in hydrophobic environments such as the interior of a molecule
 * depend on the distance between two atoms and non-symmetrical charge distribution around each
 * van der Waals contact distance is the point at which two atoms exhibit greatest attraction for each other
 * Too close and atoms repulse each other, but too far and the interaction is negligable
 * Contact point is approximately 2-3 Å
 * Energy of dissociation = ~2-4 kJ/mol

=**Water**=


 * Water affects non-covalent bonds which are important for biochemical reactions
 * Non-covalent interactions are important for biochemical reactions because they are easily reversible
 * Water is polar with asymmetric distribution of charge and highly cohesive through hydrogen bonding
 * High boiling point, heat of vaporization, heat of fusion, surface tension, internal cohesion, and dielectric constant
 * Excellent solvent for polar molecules

**Hydrophilic Effect**

 * High dielectric constant diminishes strength of electrostatic attractions between other polar molecules
 * Forms solvent (hydrated) shells around other polar molecules, creating new electrostatic fields
 * Rapid fluctuating hydrogen bond structure that allows other molecules to diffuse and interact
 * Allow high concentrations of other polar molecules to exist in water as a solution.

**Hydrophobic Effect**

 * Water interaction with non-polar molecules
 * Non-polar molecules aggregate together in water following the second law of thermodynamics to increase the total entropy of the system and release free energy
 * Hydrophobic effect promotes many biochemical reactions such as correct protein folding
 * Hydrophilic amino acids move towards the exterior
 * Hydrophobic amino acids move to the interior of the protein

=**Acids and Bases**=


 * Acid – H+ Donor
 * Strong acid produces a weak conjugate base – poor pH buffering
 * Weak acid produces a strong conjugate base – good pH buffering
 * Base – H+ Receiver
 * Strong base produces a weak conjugate acid – poor pH buffering
 * Weak base produces a strong conjugate acid – good pH buffering
 * Ka = Acid Equilibrium Constant
 * Ka = [H+][A-] / [HA]
 * [H+] remains constant when pH buffering is strong

**pH**

 * Logarithmic measure of the concentration of [H+]
 * pH = -log[H+]
 * Pure H2O at room temperature: [H+] equals [OH-] = 1 x 10-7 M
 * Therefore, -log[H+] = 7 and the pH of water is 7

**pK**

 * pK is the pH when the [conjugate acid] = [conjugate base]
 * Resistance to pH change is greatest (greatest buffering capacity)
 * pKa of an acid is the pH when [HA] = [A-]

**Henderson-Hasselbalch Equation**

 * Predicts the pH of a buffer by the –log [HA] / [A-]
 * For a weak acid, pH = pKa + log [A-] / [HA]
 * When [A-] equals [HA], the pH = pKa

**Properties of a Buffer**

 * Acid-base conjucate pair resists changes in pH of solution
 * Weak acid and strong conjugate base make a strong pH buffer
 * Bicarbonate buffer system in blood
 * Kidneys regulate H+ by renal excretion while lungs regulate CO2 by rate of ventilation
 * H+ + HCO3- <--> H2CO3 <--> H2O + CO2

=**Amino Acids**=


 * All proteins use the same set of 20 amino acids for the last several billion years
 * Amino acids vary in size, shape, charge, and chemical reactivity
 * Zwitterions (hybrid ions):
 * Amino acids in solution at physiological pH exist predominately as dipolar ions
 * Amine group is protonated (-NH3+)
 * Carboxyl group is deprotonated (-COO-)
 * Therefore, amino acid is **fully ionized** but **electrically neutral**
 * Amino acids are conjugate acid/base pairs (can be diprotic or tripotic depending on –R group)
 * Amino acid –R groups facilitate chemical reactions and form ionic bonds
 * All three pKa’s of the –COOH, -NH3+, and –R group determine the pI
 * pI is the isoelectric point which is the pH when the total net charge is zero
 * Amino acids at their isoelectric point will not move in an electric field.
 * Amino Acids have 4 different groups, (1) -NH3+, (2) –COO-, (3) –R group, (4) Hydrogen
 * Amino Acids are chiral and L-α-amino acids are constituents of proteins
 * Have an S (left) chiral configuration.


 * This is a Powerpoint slideshow with the amino acid structures (like flashcards) that Habib made in undergrad. Thought it might help someone: [[file:AAstructures.pps]]

**Non-polar, aliphatic –R groups**

 * Hydrophobic – the larger the aliphatic side chain, the more hydrophobic
 * [|Glycine]
 * Non-chiral because –R group is another hydrogen
 * [|Alanine]
 * [|Valine]
 * [|Leucine]
 * [|Isoleucine]
 * contains an additional chiral center in its –R group
 * [|Methionine]
 * contains a thioether (-S-) group and described as “polar uncharged”
 * [|Proline]
 * Aliphatic –R group is bonded to both nitrogen and α-carbon, making it conformationally restricted

**Aromatic –R groups**

 * Generally non-polar because of aromatic rings
 * [|Phenylalanine]
 * [|Tyrosine]
 * Have hydrophilic properties because of –OH group
 * Strongly absorb UV light near 280 nm, which can be used to estimate the concentration of proteins in a solution
 * [|Tryptophan]
 * Have hydrophilic properties because of –NH- group
 * Also strongly absorb UV light near 280 nm

**Aliphatic hydroxyl –R groups**

 * Hydrophilic attributes due to –OH group and stronger chemical reactivity
 * [|Serine]
 * Hydroxylated version of alanine
 * [|Threonine]
 * Like valine but with a –OH group replacing –CH3

**Aliphatic sulfhydral (thiol) –R group**

 * Polar amino acid
 * [|Cysteine]
 * -SH groups from two cysteine amino acids can form a covalently-linked cystine disulfide bridge
 * Requires an oxidation reaction
 * Similar to serine but contains a more reactive –SH group

**Basic –R groups**

 * Very polar and hydrophilic
 * -R groups are positively charged a physiological pH
 * [|Lysine]
 * [|Arginine]
 * [|Histidine]
 * Most reactive because it accepts H+

**Acidic –R groups and Uncharged derivatives**

 * Acidic side chains that are usually negatively charged at physiological pH
 * H+ Donors
 * [|Aspartate]
 * [|Glutamate]
 * [|Asparagine]
 * Uncharged derivative of Aspartate; contains a terminal carboxamide instead of carboxylic acid
 * [|Glutamine]
 * Uncharged derivative of Glutamate; contains a terminal carboxamide instead of carboxylic acid

**Non-Essential and Essential Amino Acids**

 * 11 Non-Essential Amino Acids
 * [|Alanine]
 * [|Arginine]
 * [|Asparagine]
 * [|Aspartic Acid]
 * [|Cysteine]
 * [|Glutamine]
 * [|Glutamic Acid]
 * [|Glycine]
 * [|Proline]
 * [|Serine]
 * [|Tyrosine]
 * 9 Essential Amino Acids
 * [|Histidine]
 * [|Isoleucine]
 * [|Leucine]
 * [|Lysine]
 * [|Methionine]
 * [|Phenylalanine]
 * [|Threonine]
 * [|Tryptophan]
 * [|Valine]

=**Objectives**=