Biochemistry Exam 1

Linear sequence of amino acids

Spatial arrangement of amino acids due to backbone and H-bonding. Not R groups.

The 3-D shape of the amino acids due to substituent interactions.

Connection of different protein sub-units to create the overall shape.

• The peptide bond is very rigid, giving the bond a very planar structure. This is because the peptide bond has 40% double-bond character due to resonance.
• -shorter than other bonds
• -extra pi bond overlap

• Typically trans configuration due to sterics (making it planar too)
• -10% of Pro residues are cis
• -8 kJ/mol less stable than trans

A way to describe the conformation of the peptide backbone:

• Cα - N bond Φ (counterclock)
• Cα - C bond ψ (clockwise)

Notice peptide bond not included because it is very rigid.

Angles are sterically constrained to avoid collisions with other adjacent residues.

• Indicates angles that are sterically allowed for Ψ and Φ.
• -smallest shows angles that are allowed sterically not including Gly and Pro
• -medium shows angles with very limited movement

α helix

Pro most confirmationally restricted amino acid.

Gly least sterically hindered amino acid and capable of ore freedom.

α helices and β sheets are named as such because they have repeating Φ and ψ values.

3.6 turns in a right handed manner.

Average length: 12 residues (3 turns)

It is tightly packed due to Van der Waals forces. 

The outside has side chains projecting out to reduce steric hindrance.

The backbone hydrogen bonds with each other at a distance of  2.8 Α. The lone pairs of the carboxyl group are attracted to the H of the nitrogen.

Antiparrallel: the neighboring H-bonded chains run in opposite directions. It is better this way and causes less strain on the sheet.

Parallel: H-bonded polypeptide chains run in the same direction but it does cause steric strain. They are rare and require extensive crossover of the β band.

• Range: 2-22 strands
• Average: 6 strands

Average Residues: 15 residues

This is for antiparallel strands. The numbers are much less in parallel strands.

It generally has a right handed twist to it.

The twisting causes a weakening of the H-bonding. But the twisting is a consequence of the side chain residues.

In conclusion, the twist is a compromise between optimizing conformational energies of polypeptide chain and H-bonding.

The stretch of amino acids that make sharp turns. They are what connects β sheets or α helices. It is most common in β sheets.

They are stabilized by H bonding.

• Keratin: mechanically durable and unreactive protein
• Collagen: major stress bearing component of connective tissues that is strong and insoluble

The left handed twisting of two α helices forming a coiled coil is because of the primary structure. It has a 7 amino acid repeat with nonpolar ends and 3.5 residues per turn.

Hard α keratin is rich in Cys residues to form disulfide bonds within oxidative environments.

Soft α keratin lacks many Cys residues.

These disulfide bonds are cleaved reductively.

• α keratin in humans
• β keratin in birds and reptiles

• Composed of:
• 1/3 Glycine
• 1/5 Proline
• The above amino acids are incapable of forming an α helix because there is a lack of H-bonds from Pro

It has repeating triplets of Gly, Pro, Hyp (hydroxyprolyl). The Gly is in every 3rd turn because that is when the chain moves through center of the left turn helix where only Gly can fit and the N-H can H bond with Pro carbonyl.

• Structure:
• Left handed turn oppositely twisted with crosslinks at C and N termini at the ends that increase with age.

• Irregular Coiling: coiling that appears to be random BUT is ordered (just difficult to describe)
• Random Coiling: denatured proteins, and rapidly fluctuating confirmations

When the last amino acid of the α helix cannot hydrogen bond with another amino acid causing distortion.

Causes a kink due to irregular shape and destabilize the structure

The α helices are normally surrounded by Asn and Gln that form H bonds with α helix

It destabilizes it.

Polarities

• Val (Valine)
• Leu (Leucine)
• Ile (Isoleucine)
• Met (Methionine)
• Phe (Phenylalinine)

• Arg (Arginine)
• His (Histidine)
• Lys (Lsine)
• Asp (Aspartic Acid)
• Glu (Glutamic Acid)

• Ser (Serine)
• Thr (Threonine)
• Asn (Asparagine)
• Gln (Glutamine)
• Tyr (Tyrosine)

Relaxed

Along the protein surface

• α proteins: primarily α helices
• β proteins: primarily β sheets
• α/β proteins: mix of α and β

β sheets that are plenty enough that they form a twisting barrel like structure

Portions of globular proteins that give it a multilobal appearance. These domains normally act as independent units. Layers of domains allow the protein to seal off the hydrophobic core of certain domains.

They allow flexible interactions between proteins and small molecules.

Structure and function more important than the residues.

Allows for easier subunit repair rather than having the whole molecule go to waste when damaged.

Proteins with more than one subunit.

Identical subunits.

They are stabilized by nonpolar side chains and backbone hydrogen bonding.

It has cyclic symetry commonly named C2, C3... etc depending on how many are on the same plane. Those not on the same plane and spiral up are notified as D2... etc.

To denature an amino acid residue, 0.4 kJ/mol is required to break it. This is very easy to break meaning outside forces increase protein stability.

Minimizing the the contact water has with nonpolar molecules. Having nonpolar side chains on the interior of the protein increases entropy.

The higher the hydropathy (hydrophobic / hydrophhilic tendencies) the more the residue will be in the interior.

It adds a bit of stabilizing energy by "selecting" the unique native structure of protein from among a relatively small number of hydrophobically stable conformations.

It contributes little to the stability of the molecule. The formation of the ion pair costs more entropically such that they do not compensate for their formation.

Not too much because proteins can still function without them and they are rare intracellularly.

They function to cross-link proteins.

For example, zinc can can stabilize small polypetide chain stretches through tetrahedral coordination (especially Cys, His and sometimes Asp, Glu)

It means that protein folding occurs all at once.

• -heating
• -pH change (changes charge distribution and H-bonding)
• -detergents that associate with nonpolar residues
• -chaotropic agents (ions or small molecules that increase solubility of nonpolar substances in water)

One that is rich in charged amino acids and lacks nonpolar amino acids.

But the good thing is they take up less space and become functional with transcription factors.

Proteins can fold spontaneously into native conformation under physiological conditions implying that the primary structure is responsible for protein 3D structure.

The probability of a disulfide bond reforming after RNase to proper link is around 1/105 if it was at random. This would mean that only 1% of proteins would be catalitically active.

The conformational flexibility of proteins. Proteins have more than one possible structure that can be changed by pH, oxidation state, or binding partner.

Levinthal's paradox is a thought experiment, also constituting a self-reference in the theory of protein folding. In 1969, Cyrus Levinthal noted that, because of the very large number of degrees of freedom in an unfolded polypeptide chain, the molecule has an astronomical number of possible conformations.

For example, a polypeptide of 100 residues will have 99peptide bonds, and therefore 198 different phi and psi bond angles. If each of these bond angles can be in one of three stable conformations, the protein may misfold into a maximum of 3198 different conformations (including any possible folding redundancy). Therefore, if a protein were to attain its correctly folded configuration by sequentially sampling all the possible conformations, it would require a time longer than the age of the universe to arrive at its correct native conformation.