Protein section 2

Amino acids are grouped according to their [blank_start]physico-chemical[blank_end] properties and this is reflected in the genetic code

A single base change in the [blank_start]third[blank_end] position of the codon will often produce the same amino acid and in the [blank_start]second[blank_end] position often one with very similar physico-chemical properties.

The second base of the codon specifies whether an amino acid is...

Why are conservative substitutions good

How many levels of protein structure are there

Match the level of the structure with the image

The amino acid sequence of the protein, dictated by the genetic code. This sequence contains all the information needed to specify:

Regular repeating patterns of hydrogen-bonded backbone conformations such as alpha-helices and beta-sheets.

The primary structure also dictates how these the structural elements pack together to form the overall shape of the protein in the form of folds. This is called the...

This represents the overall relative arrangement of two or more individual tertiary folded polypeptides.

Reactivities of the elements involved in the primary structure

Resonance is the result of [blank_start]delocalisation[blank_end] of [blank_start]electrons[blank_end] over several [blank_start]atoms.[blank_end]

Resonance decreases the polarity of the peptide bond and each has a dipole moment.

As we mentioned previously there is rotation allowed around [blank_start]N-Cα[blank_end] and [blank_start]Cα-C[blank_end] by angles phi and psi Thus we have a polymer with rotatable covalent bonds which alternate with rigid planar ones This [blank_start]restricts[blank_end] the number of [blank_start]conformations[blank_end] the polypeptide can adopt.

Apart from the properties of the peptide bond what other chemical reactivities does the polypeptide exhibit?

[blank_start]Hydrophobic[blank_end] side chains engage in van der Waals interactions. They have a tendency to [blank_start]avoid[blank_end] contact with water and pack against each other. This is the basis for the [blank_start]hydrophobic[blank_end] effect. Tendencies: [blank_start]Alanine[blank_end] and [blank_start]leucine[blank_end]- helix favouring residues, proline -helix breaking residue

[blank_start]Hydrophilic[blank_end] side chains are able to make [blank_start]hydrogen[blank_end] bonds with each other, with the peptide bond, with polar organic molecules and with water. Also because some are [blank_start]charged[blank_end] and exhibit [blank_start]pKa’s[blank_end] they can change their charge depending on the [blank_start]pH[blank_end] or the microenvironment.

[blank_start]Amphipathic[blank_end] side chains have both polar and non-polar character and are ideal at interfaces and may be involved in both [blank_start]H-bonding[blank_end] and [blank_start]van der Waals interactions.[blank_end]

Hydrogen bonds are formed when a hydrogen atom has a significant partial negative charge by virtue of being bound to a more electronegative atom such as oxygen or nitrogen and is attracted to a near neighbour (less than 0.35nm) that has significant partial positive charge.

The atom to which the hydrogen is attached is called the H-bond [blank_start]donor[blank_end]

The charge state of the donor and acceptor changes the strength of the H-bond.

To the right are some examples of H-bonding in proteins, the most important of which in the context of primary structure and its influence on the secondary structure of proteins is that between the amide [blank_start]donor[blank_end] and the carbonyl [blank_start]acceptor[blank_end] of the main chain peptide bond. The other shown are more important in tertiary structure.

ALTHOUGH PROTEINS ARE LINEAR POLYMERS THE STRUCTURES OF MOST OF THEM ARE NOT THE RANDOM COILS SEEN IN SYNTHETIC NON-NATURAL POLYMERS.

Most proteins are observed to be [blank_start]globular[blank_end] and have a [blank_start]tightly packed[blank_end] hydrophobic core which consists primarily of hydrophobic amino acids. One very striking feature of the folded polypeptide chain is that the chain of amino acids takes up conformations in which the torsion angles phi and psi of the backbone chain repeat in regular patterns.

Types of secondary structure

The most common of these is alpha helix

Sometimes known as pleated sheets. These sheets can exist as parallel or anti-parallel.

here the chain is forced to turn sharply in a reverse direction, this small secondary structure element allows for the compact folding of proteins.

The network of regular [blank_start]secondary[blank_end] structures contributes very significantly to the [blank_start]stability[blank_end] of the overall folded protein providing extensive networks of [blank_start]hydrogen[blank_end] bonds in which many consecutive residues are involved. All of the [blank_start]hydrogen[blank_end] bonding capability in the secondary structure of a protein is contributed from the amide nitrogen and carbonyl oxygen of the main chain peptide bond as [blank_start]donor[blank_end] and [blank_start]acceptor[blank_end] respectively. This hydrogen bonding provides much of the stabilising [blank_start]enthalpy[blank_end] which allows the polar backbone amide and carbonyl groups to exist in the very [blank_start]hydrophobic[blank_end] environment in the interior of a folded protein.

The carbonyl oxygen atom (n) of each residue accepts an H bond from the amide nitrogen four residues further along (n+5)

All of the polar amide groups of this helix are hydrogen bonded to each other except the [blank_start]first[blank_end] amide hydrogen and the [blank_start]last[blank_end] carbonyl oxygen.

The helix forms a [blank_start]cylindrical[blank_end] structure with the walls formed by the H bonded backbone with the side chains pointing [blank_start]outwards[blank_end].

What is amphipathic, in what type of secondary structure can it be seen

Steric factors favour the left handed helix.

No theoretical limit to the length of helices, very long ones up to hundreds of Angstroms have been observed in keratin (Hair protein).

formed between main chain amide hydrogen and carbonyl oxygen come from backbone groups distant from each other in the primary sequence.

The strands can run in the same direction and be parallel beta sheets or in opposite directions and be anti-parallel beta sheets. It is also possible to get mixed sheets with both parallel and anti-parallel strands together. What direction is more stable?

indicate the directionality of the sequence

Nearly all polar amide groups are [blank_start]hydrogen[blank_end] bonded to one another in a sheet structure The N-H and C=O groups on the outer sides of the sheets, the edge strands are not H bonded to other strand members. These residues can H bond to [blank_start]water[blank_end], or may pack against polar side chains in perhaps a nearby [blank_start]helix[blank_end]. [blank_start]Parallel[blank_end] sheets are always buried. Anti-parallel sheets are however frequently exposed to solvent and are probably [blank_start]more[blank_end] stable structures than parallel sheets.

parallel sheets are always separated by another structural element usually [blank_start]helices[blank_end]. beta sheet polypeptide chains are nearly fully extended (unlike helices) with distances between residues being up to [blank_start]3.3[blank_end]Angstroms. beta strands always have a pronounced [blank_start]right[blank_end] handed twist due to steric factors arising from the [blank_start]L-amino[blank_end] acid configuration. [blank_start]Valine[blank_end] and [blank_start]isoleucine[blank_end] are residues more commonly found in sheets. Beta strands can be [blank_start]amphipathic[blank_end] due to the alternating consecutive side chain configuration. These strands are found on the [blank_start]surface[blank_end] of proteins.

BETA SHEETS CANNOT FORM BARREL STRUCTURES

What kind of protein is it?

Here we see retinol binding protein with a distinct [blank_start]beta barrel[blank_end] structure. A large [blank_start]anti-parallel[blank_end] beta [blank_start]sheet[blank_end] curves all the way round with the last strand [blank_start]hydrogen[blank_end] bonded to the first thus forming a closed cylinder. The interior of the cylinder is lined with [blank_start]hydrophobic[blank_end] residues and can accommodate retinol which is [blank_start]non-polar[blank_end].

The simplest secondary structural element is the beta turn and usually involves just [blank_start]four[blank_end] residues. It is very important in allowing compact folding of proteins and is often found connecting the strands of [blank_start]anti-parallel[blank_end] beta sheets. The beat turn comprises a hydrogen bond from the carbonyl oxygen of one residue (n) to the amide N-H of residue [blank_start]n+3[blank_end]. This reverses the direction of the chain. Beta turn are most commonly found on the [blank_start]surface[blank_end] of proteins in contact with the aqueous environment. The tight geometry of the turn means that some amino acids such as [blank_start]glycine[blank_end] are found more commonly in turns than other bulkier groups.

What limits the number and positioning of secondary structural elements