Proteins and enzymes, Section 2, levels of structure (Dr. Taylorson)

Question 1

What dictates proteins sequence structure and properties ?

Answer 1

The genetic code. This makes proteins the most versatile molecules.

Question 2

What are the 4 levels of proteins structure ?

Answer 2

Primary : AA sequence
Secondary : repeating patterns of H-bonded backbone conformations (helices and sheets)
Tertiary: the overall folded secondary structural elements
Quaternary: the overall relative arrangement of 2 or more individual tertiary folded polypeptides
2ary, 3ary and 4ary structures are all dictated by the primary structure itself.

Question 3

Why does the peptide bond have partial double bond character ?
How does this affect the polypeptide chain ?

Answer 3

Because of the two different resonance structure of this bond. Thus, the carboxyl O, the C and the N are coplanar. This restricts the number of conformations the polypeptide can adopt.

Question 4

What is resonance ?

How does this affect the amide bond ?

Answer 4

Resonance is the result of delocalization of electrons over several atoms.
The increases the polarity of the amide bond and each has a dipole moment.

Question 5

How long are H-bonds (approximately) in proteins ?

Answer 5

H-bonds in proteins, such as the amide-carbonyls (peptide bond), amide-imidazole, hydroxyl-carbonyl, hydroxyl-hydroxyl, are between 0.28 and 0.31nm.

Question 6

Which characteristics are repeatedly observed in proteins ?

Answer 6

A globular structure with a tightly packed hydrophobic core which consists primarily of hydrophobic amino acids.

Question 7

What are the characteristics of the torsion angles Phi and Psi of the polypeptide chain ?

Answer 7

They repeat in regular patterns.

Question 8

What are the three general types of secondary structures ?

Answer 8

Helices: most common is the alpha helix (but also i+3 helices to lesser extent)
Beta sheets: pleated sheets, parallel or anti-parallel
Beta turns

Question 9

What is the main interaction that contribute to the overall stability of the folded polypeptide ?

Answer 9

H-bonding (always from amide nitrogen and carbonyl oxygen, some R groups sometimes).
H-bonding provides much of the stabilizing enthalpy which allows the polar backbone amide and carbonyl groups to exist in the very hydrophobic environment in the interior of a folded protein.

Question 10

How are alpha helices formed ?

Answer 10

By local H-bonding between the carbonyl oxygen (acceptor) and the amide nitrogen (donor) 4 residues further along.
ALL of the polar amide groups of the alpha helix are H-bond to each other, except for the first amide and last carbonyl oxygen.

Question 11

Why is proline a helix breaker ?

Answer 11

Proline’s amide nitrogen is bonded to its own side chain; it thus cannot form a H-bond with the carbonyl group 4 residues further up.

Question 12

How are the R groups of the alpha helix orientated ?

Why is this significant ?

Answer 12

Outwards.
These protruding side chains determine the interactions of the helix with other parts of the protein chain and with other molecules.
The nature of the AAs in the helix means under some circumstances the helix can be amphipathic by exhibiting hydrophobic nature on one side and hydrophilic on the other.

Question 13

Is the right-handed or the left-handed helix favored in nature ?
Why ?

Answer 13

Steric factors favour the right handed-helix.

Question 14

Is there a limit to the alpha helix’s length ?

Answer 14

Theoretically, no. Very long ones can be hundreds of angstroms in length (keratin).

Question 15

Why is the beta pleated sheets called like this ?

Answer 15

Because of the pleated or corrugated appearance of the extended polypeptide chain.

Question 16

How are the beta sheet strands arranged ?

Answer 16

these are arranged side by side w/ H-bonds between the strands.

Question 17

What are the two main types of beta sheets ?

Answer 17

Parallel (non-linear H-bond) and anti-parallel (liner H-bonds).
Some sheets can be mixed.

Question 18

If the N-H and C=O groups on the outer sides of the sheets are not H-bonded to other strand members, what do they do ?

Answer 18

These residues can H-bond to water, or may pack against a polar side chains in perhaps a nearby helix.

Question 19

Where are parallel and anti-parallel sheets found.

Answer 19

Parallel sheets are ALWAYS BURIED.

Anti-parallel sheets are frequently exposed to solvent and are probably more stable features than parallel sheets.

Question 20

What usually septettes parallel sheets ?

Answer 20

Helices.

Question 21

Are beta sheets extended like helices ?

Answer 21

NO !

Beta sheets polypeptide chains are nearly fully extended, with distance between residues being up to 3.3 angstroms.

Question 22

To beta sheets have a preferred twist ?

Answer 22

Yes, a pronounced right hand twist, due to steric facts arising from the L-AA configuration.

Question 23

Which residues are found more commonly in beta sheets ?

Answer 23

Valine and isoleucine (both aliphatic) predominantly,

but also Tye, Cis, Trp, Phe, Thr.

Question 24

How can beta sheets be amphipathic ?

Answer 24

By having alternating consecutive side chain configurations.

Question 25

Where are beta sheets generally found ?

Answer 25

On the surface of proteins.

Question 26

What is the structure retinol binding protein ?

Answer 26

A large anti-parallel beta sheet curves all the way round with the last strand H-bonded to the first thus forming a closed cylinder.
The interior of the cylinder is lined with hydrophobic residues to accommodate retinol which is non-polar.

Question 27

What is the beta turn ?

Answer 27

The beta turn is the simplest of secondary structural element and usually involves just 4 residues. It comprises a H-bond from the carbonyl O of one residue (n) to the amide N-H of residue n+3. This reverses the direction of the chain.

Question 28

Where are beta turns most commonly found and why are they important ?

Answer 28

They are most commonly found on the surface of proteins in contact with the aqueous environment, connecting the strands of anti-parallel beta sheets. They are very important in allowing compact folding of proteins.

Question 29

Which amino acids are found in the beta turn ?

What does this imply ?

Answer 29

Glycine (smallest AA) and proline (helix breaker) are always in beta turns. This is due to the turns tight geometry.
There are also other AAs often found in turns such as Asn, Ser, and Asp.
Having such small and flexible amino acids can make the beta turn a favorable binding site.

Question 30

Which amino acids are more often found in alpha helices ?

Answer 30

Glu, Ala, Leu, Met, Gln, Lys, Arg, His.

Question 31

What is the difference between a turn and a loop ?

Answer 31

A loop is a much larger and less ordered structure, linking 2dary structural elements. It also exhibits flexibility and is often involved in binding events.