Proteins Note
Function of proteins (rely of 3D structure):
• Enzymes (+communication) • Build up structures eg.collagen
• Transport + storage nutrients eg. • Defense/antibodies
Hb
Proteins are made up from 20 amino acids which consist of C, O, N, H and some contain S
atoms
Selenocysteine is the only standard amino acid that contains a selenium (Sel) atom and it’s
the 21st amino acid Se
Amino acid is made up of carboxyl
group, amino group and side chain
attached to the central carbon atom
At physiological pH, the amino acid is charged
Side chain is the only thing that varies/is specific between diff amino acids and it gives its
unique properties eg. Hydrophobic/non-polar (carbon-rich)+ aliphatic or aromatic,
hydrophilic + uncharged or charged +vely or -vely(interact with oppositely charged amino
acids or other molecules) - Classification is based on R-group
-carbon is chiral (enantiomers which
exist as mirror images of one another)
and function/properties differ by its
stereoisomerism; when shine polarised
light to the molecule, the light gets diffracted towards right or left; D (dextrorotation)- rotates
to left while L (laevorotation) - rotates to right; most amino acids in our body are in L form
and all amino acids incorporated into protein is L form
Primary structure is linear sequence of amino acids encoded by
DNA - the -carboxyl is joined to -amino of different amino acid
with removal of water. The peptide group and C make up the
polypeptide backbone/main-chain (R-group carboxyl or amino
groups are not included)
Peptide group
, Resonance structure
peptide bond is planar
• Oxygen is slightly negative, while the
nitrogen is slightly positive - due to this
uneven distribution of charge the C-N bond gains
some double bond character. Delocalisation makes
the bond shorter than you would expect
for a single bond but, more importantly,
it makes it difficult to rotate and it forces
the six atoms involved in the peptide link
into a single plane.
• The freedom of the Ca - CO and N -
Ca bonds to rotate is not restricted in
this way, but rotation may be limited
by steric factors. This is where particular
rotations would cause atoms to collide
with each other. In general large side chain groups restrict bond rotation more than small
groups. Rotations that bring together the oxygens or hydrogens from adjacent peptide
links are unlikely to occur.
• Resonance structures are two forms of a molecule where the chemical connectivity is the
same but the electrons are distributed differently around the structure so electrons flow
through neighbouring pi system.
• This resonance restricts the number of conformations in proteins:
main chain rotations are restricted to and . The conformations
of peptides are defined by the values of and .
Ramachandran plot
✓ Shows what sort of secondary structures you might get
✓ Physical size of atoms and groups of atoms limits the
possible psi and phi torsion angles that the backbone of
the polypeptide chain can adopt without causing
protruding R-groups to bump into each other
✓ Possible conformation: red patches above are those
combinations of psi and phi angles that are allowed as they do not result in steric
hinderance - yellow areas are allowed with a little relaxation of steric hinderance and the
, rest are impossible for all amino acids except glycine which is unique since it lacks a side
chain
✓ Combination of angles found in certain secondary structure
Amino acid polymers
Oligopeptide - short polymer of amino acids linked
by peptide bonds; up to 50 residues
o (-)Endorphin – produced when exercised –
acts as a natural painkiller and they interact
with receptors in the brain to inhibit the
transmission of pain signals – allow continue of functioning even when you are under
the strain – contains 16 amino acid residues
o Oxytocin – first synthetic oligopeptide made – no need to purify this – produced by
pituitary gland and stimulates uterine contractions in labour – contains 9 amino acid
residues
o Glutathione – (=-glutamyl-L-cysteinylglycine) tripeptide where -carboxyl group of
glutamic acid residue (not α-carboxyl group) contributes to the peptide bond –
reducing agent – involved in protecting cells from destructive effects of oxidation
o Name based on their activities/biological functions
Polypeptide - longer polymer of amino acids linked by peptide bonds; larger sizes
Protein - one or more polypeptide chains
Primary structure provide information related to protein evolution:
o Evolution conserves amino acids that are important to protein structure and function –
in sequence comparison of proteins with same function/from same structure would
have a highly conserved regions that are important for function
o Clusters of conserved residues are called motifs carry out a particular function or form
a particular structure
Motif with invariant and conservative amino acid
substitution
❖ Invariant = the residue that is always the same
❖ Conserved = the residue is generally similar (eg.
Small hydrophobic/ large hydrophobic/ polar/
positive charge/ negative charge)
❖ Not conserved = can be many different residues in
different species
❖ Generally only a limited amount of a protein’s
, surface is well conserved
❖ Area which is conserved is restricted
❖ Eg. Specific hormones have key residue/motif for part of the sequence responsible for
signalling and binding
❖ Based on the difference/similarity of the amino acid sequences for particular molecule
are, we can plot a phylogenetic relationship – branch distances indicate amino acid
sequence divergence
proline has a side chain which is an alkyl group that wraps around and forms a second
covalent bond with the nitrogen atom of backbone so it has secondary alpha amino group –
hard to form secondary structure
Secondary structure - fold into two types: alpha helices (it’s a right-handed coil stabilized by
hydrogen bonds between the amine and carboxyl group of nearby amino acids) or beta sheet
(formed when hydrogen bonds stabilize two or more adjacent strands of amino acids) –
spatial arrangement of protein by twisting of the polypeptide chain
Hydrogen bonding – occurs between H and O/N/F; EN atoms are slightly negatively charged
while H is slightly positively charged (electron pair is closer to EN atom); draw the bond with
dashed line
Folding patterns
-helix β–pleated sheet
made up of amino acids with small side chains - protein fold itself into ribbon - generally fibrous/rod like
backbone becomes a spiral and side chain extend shaped and are not so soluble in water
outwards - Torsion angles phi and psi of the backbone carbonyl oxygens and amides of another amino acid
chain repeat in regular patterns - Most common and form H bonds (near perpendicular to direction of peptide
stable conformation - R-group side chains are stabilized backbone)
by H bonding between carbonyl oxygen and amide adjacent chains can be either antiparallel or parallel and
hydrogen - H bonds are individually weak but can be planar or twisted – parallel: H bonds between 2
collectively strong enough chains running in the same direction whereas anti-
Overall dipole moment = positively charged N-terminus parallel: H bonds between 2 chains running in opposite
to negatively charged C-terminus ; helix can be directions
amphipathic The propensity of peptide for forming beta sheet also
Helices can be right or left handed but proteins are right depends on its sequence
handed (steric factor favour the right) Unlike α-helix, β-sheet can involve one or more
The propensity (tendency) of peptide for forming an α- polypeptide chains resulting interchain or intrachain
helix also depends on its sequence interactions; unlike the local interactions in helices, it is
the side chains determine the interactions of the helix composed of long-range interactions: adjacent strands
with other parts of the protein chain and with other can come from completely different sections of
molecules polypeptide chain or even different polypeptides
R groups stick up and down from β-sheets
Distance between adjacent amino acid is 3.5 Angstroms -
as chains are nearly fully extended
Function of proteins (rely of 3D structure):
• Enzymes (+communication) • Build up structures eg.collagen
• Transport + storage nutrients eg. • Defense/antibodies
Hb
Proteins are made up from 20 amino acids which consist of C, O, N, H and some contain S
atoms
Selenocysteine is the only standard amino acid that contains a selenium (Sel) atom and it’s
the 21st amino acid Se
Amino acid is made up of carboxyl
group, amino group and side chain
attached to the central carbon atom
At physiological pH, the amino acid is charged
Side chain is the only thing that varies/is specific between diff amino acids and it gives its
unique properties eg. Hydrophobic/non-polar (carbon-rich)+ aliphatic or aromatic,
hydrophilic + uncharged or charged +vely or -vely(interact with oppositely charged amino
acids or other molecules) - Classification is based on R-group
-carbon is chiral (enantiomers which
exist as mirror images of one another)
and function/properties differ by its
stereoisomerism; when shine polarised
light to the molecule, the light gets diffracted towards right or left; D (dextrorotation)- rotates
to left while L (laevorotation) - rotates to right; most amino acids in our body are in L form
and all amino acids incorporated into protein is L form
Primary structure is linear sequence of amino acids encoded by
DNA - the -carboxyl is joined to -amino of different amino acid
with removal of water. The peptide group and C make up the
polypeptide backbone/main-chain (R-group carboxyl or amino
groups are not included)
Peptide group
, Resonance structure
peptide bond is planar
• Oxygen is slightly negative, while the
nitrogen is slightly positive - due to this
uneven distribution of charge the C-N bond gains
some double bond character. Delocalisation makes
the bond shorter than you would expect
for a single bond but, more importantly,
it makes it difficult to rotate and it forces
the six atoms involved in the peptide link
into a single plane.
• The freedom of the Ca - CO and N -
Ca bonds to rotate is not restricted in
this way, but rotation may be limited
by steric factors. This is where particular
rotations would cause atoms to collide
with each other. In general large side chain groups restrict bond rotation more than small
groups. Rotations that bring together the oxygens or hydrogens from adjacent peptide
links are unlikely to occur.
• Resonance structures are two forms of a molecule where the chemical connectivity is the
same but the electrons are distributed differently around the structure so electrons flow
through neighbouring pi system.
• This resonance restricts the number of conformations in proteins:
main chain rotations are restricted to and . The conformations
of peptides are defined by the values of and .
Ramachandran plot
✓ Shows what sort of secondary structures you might get
✓ Physical size of atoms and groups of atoms limits the
possible psi and phi torsion angles that the backbone of
the polypeptide chain can adopt without causing
protruding R-groups to bump into each other
✓ Possible conformation: red patches above are those
combinations of psi and phi angles that are allowed as they do not result in steric
hinderance - yellow areas are allowed with a little relaxation of steric hinderance and the
, rest are impossible for all amino acids except glycine which is unique since it lacks a side
chain
✓ Combination of angles found in certain secondary structure
Amino acid polymers
Oligopeptide - short polymer of amino acids linked
by peptide bonds; up to 50 residues
o (-)Endorphin – produced when exercised –
acts as a natural painkiller and they interact
with receptors in the brain to inhibit the
transmission of pain signals – allow continue of functioning even when you are under
the strain – contains 16 amino acid residues
o Oxytocin – first synthetic oligopeptide made – no need to purify this – produced by
pituitary gland and stimulates uterine contractions in labour – contains 9 amino acid
residues
o Glutathione – (=-glutamyl-L-cysteinylglycine) tripeptide where -carboxyl group of
glutamic acid residue (not α-carboxyl group) contributes to the peptide bond –
reducing agent – involved in protecting cells from destructive effects of oxidation
o Name based on their activities/biological functions
Polypeptide - longer polymer of amino acids linked by peptide bonds; larger sizes
Protein - one or more polypeptide chains
Primary structure provide information related to protein evolution:
o Evolution conserves amino acids that are important to protein structure and function –
in sequence comparison of proteins with same function/from same structure would
have a highly conserved regions that are important for function
o Clusters of conserved residues are called motifs carry out a particular function or form
a particular structure
Motif with invariant and conservative amino acid
substitution
❖ Invariant = the residue that is always the same
❖ Conserved = the residue is generally similar (eg.
Small hydrophobic/ large hydrophobic/ polar/
positive charge/ negative charge)
❖ Not conserved = can be many different residues in
different species
❖ Generally only a limited amount of a protein’s
, surface is well conserved
❖ Area which is conserved is restricted
❖ Eg. Specific hormones have key residue/motif for part of the sequence responsible for
signalling and binding
❖ Based on the difference/similarity of the amino acid sequences for particular molecule
are, we can plot a phylogenetic relationship – branch distances indicate amino acid
sequence divergence
proline has a side chain which is an alkyl group that wraps around and forms a second
covalent bond with the nitrogen atom of backbone so it has secondary alpha amino group –
hard to form secondary structure
Secondary structure - fold into two types: alpha helices (it’s a right-handed coil stabilized by
hydrogen bonds between the amine and carboxyl group of nearby amino acids) or beta sheet
(formed when hydrogen bonds stabilize two or more adjacent strands of amino acids) –
spatial arrangement of protein by twisting of the polypeptide chain
Hydrogen bonding – occurs between H and O/N/F; EN atoms are slightly negatively charged
while H is slightly positively charged (electron pair is closer to EN atom); draw the bond with
dashed line
Folding patterns
-helix β–pleated sheet
made up of amino acids with small side chains - protein fold itself into ribbon - generally fibrous/rod like
backbone becomes a spiral and side chain extend shaped and are not so soluble in water
outwards - Torsion angles phi and psi of the backbone carbonyl oxygens and amides of another amino acid
chain repeat in regular patterns - Most common and form H bonds (near perpendicular to direction of peptide
stable conformation - R-group side chains are stabilized backbone)
by H bonding between carbonyl oxygen and amide adjacent chains can be either antiparallel or parallel and
hydrogen - H bonds are individually weak but can be planar or twisted – parallel: H bonds between 2
collectively strong enough chains running in the same direction whereas anti-
Overall dipole moment = positively charged N-terminus parallel: H bonds between 2 chains running in opposite
to negatively charged C-terminus ; helix can be directions
amphipathic The propensity of peptide for forming beta sheet also
Helices can be right or left handed but proteins are right depends on its sequence
handed (steric factor favour the right) Unlike α-helix, β-sheet can involve one or more
The propensity (tendency) of peptide for forming an α- polypeptide chains resulting interchain or intrachain
helix also depends on its sequence interactions; unlike the local interactions in helices, it is
the side chains determine the interactions of the helix composed of long-range interactions: adjacent strands
with other parts of the protein chain and with other can come from completely different sections of
molecules polypeptide chain or even different polypeptides
R groups stick up and down from β-sheets
Distance between adjacent amino acid is 3.5 Angstroms -
as chains are nearly fully extended
