Amino acids are grouped according to their physico-chemical
biological( physico-chemical, binding, structural, biological ) properties and this is reflected in the genetic code
A single base change in the third
second( third, first, second ) position of the codon will often produce the same amino acid and in the second
first( second, third, first ) position often one with very similar physico-chemical properties.
The second base of the codon specifies whether an amino acid is...
polar or hydrophobic
basic or acidic
primary or secondary
aromatic or non-aromatic
Why are conservative substitutions good
because of them mutation events in the DNA sequence do not lead to a change in the function
they induce molecular evolution
they repair DNA
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
The overall polypeptide chain
The peptide bond
The amino acid R groups of the primary structure
The size of the amino acid sequence
Resonance is the result of delocalisation
protonation( delocalisation, deprotonation, protonation ) of electrons
hydrogen atoms( electrons, side chains, hydrogen atoms ) over several atoms
molecules( atoms, molecules )
Resonance decreases the polarity of the peptide bond and each has a dipole moment.
As we mentioned previously there is rotation allowed around N-Cα
N-Cb( N-Cα, N-Cb ) and Cα-C
Cb-C( Cα-C, Cb-C ) by angles phi and psi
Thus we have a polymer with rotatable covalent bonds which alternate with rigid planar ones
increases( restricts, increases ) the number of conformations
bonds( conformations, bonds ) the polypeptide can adopt.
Apart from the properties of the peptide bond what other chemical reactivities does the polypeptide exhibit?
The reactivity of the carbonyl oxygen and amide nitrogen of the peptide bond
The various reactivities of the R groups attached to the α-carbon of the amino acids in the primary structure.
The London dispersion interactions between the amino acids
Hydrophilic( Hydrophobic, Hydrophilic ) side chains engage in van der Waals interactions. They have a tendency to avoid
go into( avoid, go into ) contact with water and pack against each other. This is the basis for the hydrophobic
hydrophilic( hydrophobic, hydrophilic ) effect.
Serine( Alanine, Methionine, Serine ) and leucine
Histidine( leucine, Aspargine, Histidine )- helix favouring residues, proline -helix breaking residue
Hydrophobic( Hydrophilic, Hydrophobic ) side chains are able to make hydrogen
covalent( hydrogen, covalent ) bonds with each other, with the peptide bond, with polar organic molecules and with water. Also because some are charged
neutral( charged, neutral ) and exhibit pKa’s
pH( pKa’s, pH ) they can change their charge depending on the pH
pKa( pH, pKa ) or the microenvironment.
Basic( Amphipathic, Acidic, Basic ) side chains have both polar and non-polar character and are ideal at interfaces and may be involved in both H-bonding
Covalent bonding( H-bonding, Covalent bonding ) and van der Waals interactions.
hydrophobic interactions( van der Waals interactions., hydrophobic interactions )
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 donor
acceptor( donor, acceptor )
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 donor
acceptor( donor, acceptor ) and the carbonyl acceptor
donor( acceptor, donor ) 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 and have a 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 secondary
primary( secondary, primary ) structures contributes very significantly to the stability
size( stability, conformation, size ) of the overall folded protein providing extensive networks of hydrogen
covalent( hydrogen, covalent ) bonds in which many consecutive residues are involved. All of the hydrogen
covalent( hydrogen, covalent ) 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 donor
acceptor( donor, acceptor ) and acceptor
donor( acceptor, donor ) respectively.
This hydrogen bonding provides much of the stabilising enthalpy
entropy( enthalpy, entropy ) which allows the polar backbone amide and carbonyl groups to exist in the very hydrophobic
hydrophylic( hydrophobic, hydrophylic ) 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 amide hydrogen and the carbonyl oxygen.
The helix forms a cylindrical
spherical( cylindrical, tetrahedral, spherical ) structure with the walls formed by the H bonded backbone with the side chains pointing outwards
inwards( outwards, inwards ).
What is amphipathic, in what type of secondary structure can it be seen
hydrophobic nature on one side of the helix and hydrophilic on the other; helices
hydrophobic nature on one side of the helix and hydrophilic on the other; beta turns
acidic nature on one side of the helix and basic on the other; beta sheets
acidic nature on one side of the helix and basic hydrophilic on the other; coils
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 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 , or may pack against polar side chains in perhaps a nearby .
sheets are always buried.
Anti-parallel sheets are however frequently exposed to solvent and are probably stable structures than parallel sheets.
parallel sheets are always separated by another structural element usually .
beta sheet polypeptide chains are nearly fully extended (unlike helices) with distances between residues being up to Angstroms.
beta strands always have a pronounced handed twist due to steric factors arising from the acid configuration.
and are residues more commonly found in sheets.
Beta strands can be due to the alternating consecutive side chain configuration. These strands are found on the of proteins.
BETA SHEETS CANNOT FORM BARREL STRUCTURES
What kind of protein is it?
Here we see retinol binding protein with a distinct beta barrel
alpha helix( beta barrel, alpha helix ) structure.
A large anti-parallel
parallel( anti-parallel, parallel ) beta sheet
turns( sheet, turns ) curves all the way round with the last strand hydrogen
nitrogen( hydrogen, nitrogen ) bonded to the first thus forming a closed cylinder.
The interior of the cylinder is lined with hydrophobic
hydrophylic( hydrophobic, hydrophylic ) residues and can accommodate retinol which is non-polar
polar( non-polar, polar ).
The simplest secondary structural element is the beta turn and usually involves just four
five( four, five ) residues. It is very important in allowing compact folding of proteins and is often found connecting the strands of anti-parallel
parallel( anti-parallel, parallel ) beta sheets.
The beat turn comprises a hydrogen bond from the carbonyl oxygen of one residue (n) to the amide N-H of residue n+3
n+4( n+3, n+4 ). This reverses the direction of the chain.
Beta turn are most commonly found on the surface
interior( surface, interior ) of proteins in contact with the aqueous environment.
The tight geometry of the turn means that some amino acids such as glycine
glutamine( glycine, phenylalanine, glutamine ) are found more commonly in turns than other bulkier groups.
What limits the number and positioning of secondary structural elements
size of R group
nature of R group
The amount of peptide bonds