1.

Cells
2. Chemical Principles

3. Protein Structure
4. Protein Function

5. DNA Structure
6. Chromosomes

7. Replication
8. Repair and Recombination

9. RNA
10. Protein synthesis
Protein Structure
Amino acids and primary structure
Secondary structure
Tertiary and quaternary structure

Protein Function
Binding and antibodies
Catalysis and enzymes
Mechanical machines
BIOPOLYMERS
The central dogma of molecular biology
 What is a protein?

• A protein is a linear polymer of amino acids linked

together by peptide bonds.
• The average protein is ~200 amino acids long, but
some can contain thousands of amino acids.
• Proteins are the main functional chemicals in the
cell, carrying out many functions.
• Proteins have a complex structure which can be
thought of as having four structural levels.
04_09_Proteins.jpg
 What do different proteins do?
1. Enzymes
catalysts of various biochemical reactions
e.g. lactase catalyses the breakdown of lactose into glucose and galactose
(no lactase and you’re lactose intolerant)
2. Hormones
co-ordinate bodily activities
e.g. insulin regulates blood sugar level (if not, diabetes)
3. Receptors
Involved in cellular signalling
e.g. beta-adrenergic receptor responds to adrenaline
4. Defensive proteins
defence against pathogens
e.g. antibodies combat bacteria and viruses
 What do different proteins do?
5. Structural proteins
provide structure and support
e.g. collagen in tendons and ligaments, keratin in
hair and nail
6. Storage proteins
e.g. store amino acids; ovalbumin in egg white

7. Contractile proteins
form structures that create movements
e.g. actin fibres in muscles
8. Transport proteins
transport things around body or across membranes
e.g. haemoglobin carries O2 from lung to other body parts
What is an amino acid?

The main backbone of every

amino acid is the same. This
forms the backbone of the
polypeptide chain.

It is the R-group (which

projects out from the
backbone) that makes each of
the twenty kinds of amino
acids unique.

Different amino acids have

different properties that affect
the folding of a protein.
 R group diversity

The 20 common amino acids have R groups that differ from

each other in the following way:

• Polarity: hydrophobic or hydrophilic or charged

• Charge: positive or negative

• Chemical property: different functional groups

• Size: big or small

• Shape: flat or round

 Amino acid classification

There are 5 groups according to the R group's polarity:

• Nonpolar aliphatic - hydrophobic (i.e. water-hating)

• Aromatic R Group - hydrophobic

• Polar, uncharged - hydrophilic (i.e. water-loving)

• Positively charged - hydrophilic

• Negatively charged - hydrophilic

Non-polar Side chains

The side chain of proline is bonded to both the nitrogen and alpha carbon. The resulting structure
influence protein architecture. Proline is often found in bends of folded proteins. Proline has a
secondary amino group which makes it an imino acid
Uncharged polar side chains
04_29_Disulfide bonds.jpg
Acidic Side Chains
Basic Side Chains

Histidine is often found in the active

site of enzymes where the imidazole
ring can readily switch between states
to catalyse reactions
Each amino acid has a three letter code and a
single letter code:

Alanine Ala A Methionine Met M

Cysteine Cys C Asparagine Asn N

Aspartic Acid Asp D Proline Pro P

Glutamic Acid Glu E Glutamine Gln Q

Phenylalanine Phe F Arginine Arg R

Glycine Gly G Serine Ser S

Histidine His H Threonine Thr T

Isoleucine Ile I Valine Val V

Lysine Lys K Tryptophan Trp W

Leucine Leu L Tyrosine Tyr Y

 Protein Structure
Most proteins are folded into a complex globular shape. Each protein
molecule consists of one or more chains of amino acid monomers. The
amino acids are linked by peptide bonds, so a protein polymer is often
called a polypeptide. Because they are so complicated, proteins are
usually described in terms of four levels of structure.
 Primary structure
A protein’s primary structure is the order of amino acids in
the chain. Conventionally written from the (amino) N-
terminal to the (carboxyl) C-terminal.

e.g.
using three letter codes; SER ASP LYS ILE ILE HIS LEU THR ASP ASP SER PHE ASP
or using one letter codes; SDKIIHLTDDSPD

This sequence contains all the information required to determine

the higher levels of structure. The linear polypeptide chain folds
in a particular arrangement, giving a three-dimensional structure.
The information on how to fold is contained in the sequence.
 Protein Structure
Proteins are polymers
of amino acids.

The peptide bond is planar.

Rotation around the alpha-

carbons leads to a large
number of possible
conformations.
04_01_peptide bonds.jpg
04_02_polypeptide back.jpg
04_05_Hydrophobic.jpg
 Quiz
Which of the following statements is TRUE?
(a) Peptide bonds are the only covalent bonds that can
link together two amino acids in proteins.
(b) The polypeptide backbone is free to rotate about
each peptide bond.
(c) Nonpolar amino acids tend to be found in the
interior of proteins.
(d) The sequence of the atoms in the polypeptide
backbone varies between different proteins.
(e) A protein chain ends in a free amino group at the C-
terminus.
 Quiz
Which of the following statements is TRUE?
(a) Peptide bonds are the only covalent bonds that can
link together two amino acids in proteins. FALSE
(b) The polypeptide backbone is free to rotate about
each peptide bond.
(c) Nonpolar amino acids tend to be found in the
interior of proteins.
(d) The sequence of the atoms in the polypeptide
backbone varies between different proteins.
(e) A protein chain ends in a free amino group at the C-
terminus.
 Quiz
Which of the following statements is TRUE?
(a) Peptide bonds are the only covalent bonds that can
link together two amino acids in proteins. FALSE
(b) The polypeptide backbone is free to rotate about
each peptide bond. FALSE
(c) Nonpolar amino acids tend to be found in the
interior of proteins.
(d) The sequence of the atoms in the polypeptide
backbone varies between different proteins.
(e) A protein chain ends in a free amino group at the C-
terminus.
 Quiz
Which of the following statements is TRUE?
(a) Peptide bonds are the only covalent bonds that can
link together two amino acids in proteins. FALSE
(b) The polypeptide backbone is free to rotate about
each peptide bond. FALSE
(c) Nonpolar amino acids tend to be found in the
interior of proteins. TRUE
(d) The sequence of the atoms in the polypeptide
backbone varies between different proteins.
(e) A protein chain ends in a free amino group at the C-
terminus.
 Quiz
Which of the following statements is TRUE?
(a) Peptide bonds are the only covalent bonds that can
link together two amino acids in proteins. FALSE
(b) The polypeptide backbone is free to rotate about
each peptide bond. FALSE
(c) Nonpolar amino acids tend to be found in the
interior of proteins. TRUE
(d) The sequence of the atoms in the polypeptide
backbone varies between different proteins. FALSE
(e) A protein chain ends in a free amino group at the C-
terminus. FALSE
 Secondary structure
A regular repetitive conformation of the
polypeptide chain, stabilised by hydrogen bonding
between backbone NH and C=O. The three
dominant forms are;
α Helix
Loop
helix
sheet
loops

β Sheet
Turn
 α-helix
The carbonyl
oxygen of residue n
hydrogen bonds to
the backbone -NH
of the residue n+4.
Side-chains point
away from the
helix axis.
 α-helix
The carbonyl
oxygen of residue n
hydrogen bonds to
the backbone -NH
of the residue n+4.
Side-chains point
away from the
helix axis.
 α-helix
The carbonyl
oxygen of residue n
hydrogen bonds to
the backbone -NH
of the residue n+4.
Side-chains point
away from the
helix axis.
α-helix
04_10_1_alpha h. beta s.jpg
 β-sheet
Sheet is held
together by
hydrogen bonding
across the strands.
Side-chains alternate
between pointing up
and down.
 β-sheet
Sheet is held
together by
hydrogen bonding
across the strands.
Side-chains alternate
between pointing up
and down.
 β-sheet
Sheet is held
together by
hydrogen bonding
across the strands.
Side-chains alternate
between pointing up
and down.
β-sheet
04_10_2_alpha h. beta s.jpg
 loops

Loops join the other

elements of secondary
structure. They are
often solvent exposed.

e.g. thioredoxin has a five stranded beta-

sheet flanked with alpha-helices.
Relative probability that a given amino acid will
occur in the three common types of
secondary structure

Amino acid sequence affects helix

and β sheet stability

Bulky shape of Asn, Cys, Ser, Thr

can destabilise the helix if they
are close together in a chain.

Proline introduces a destabilising

kink in α helices.

Gly occurs infrequently in α

helices and β sheets as it is very
flexible.
Super secondary structure
Recognisable combinations
(motifs) of secondary structure

βαβ

All β αα corner or helix

turn helix
 Tertiary structure
Describes how elements
of secondary structure
associate to give an
overall protein structure.
Driven by hydrophobic
interactions in the
protein core, salt bridges
and, occasionally,
disulphide bonds.
 Tertiary structure
Describes how elements
of secondary structure
associate to give an
overall protein structure.
Driven by hydrophobic
interactions in the
protein core, salt bridges
and, occasionally,
disulphide bonds.
 Domains in tertiary structure
Domains are subdivisions of tertiary structure and
are incorporated as modules into proteins.
β-sandwich
helix bundles Parallel β-barrel
- α/β sequence

Structural domains
can be composed of Myohemerythrin Prealbumin
anything between 25-
anti-parallel
300 amino acids. They β -sheet
Pyruvate Kinase domain 1
are often made up of twisted β-sheet
a combination of
motifs

Tobacco mosaic Immunoglobulin Hexokinase domain2

coat protein V2 domain
04_19_functiondomains.jpg
 Quaternary structure
The organisation of
individual protein
subunits into larger
complexes.

Stabilised by the same

types of interaction
that stabilise tertiary
structure
04_24_complexstructure.jpg
04_26_spherical shell.jpg
 Quaternary structure
A 90nm diameter
viral shell formed
from an array of
trimers of a single
capsid protein.

chlorella; 5040
copies of a single
protein form the
shell
 Identify the three types of secondary structure
labeled below (I, II, III) and briefly describe
forces that stabilize them. II
I

III
Protein Structure
 What do different proteins do?
1. Enzymes
catalysts of various biochemical reactions
e.g. lactase catalyses the breakdown of lactose into glucose and galactose
(no lactase and you’re lactose intolerant)
2. Hormones
co-ordinate bodily activities
e.g. insulin regulates blood sugar level (if not, diabetes)
3. Receptors
Involved in cellular signalling
e.g. beta-adrenergic receptor responds to adrenaline
4. Defensive proteins
defence against pathogens
e.g. antibodies combat bacteria and viruses
 What do different proteins do?
5. Structural proteins
provide structure and support
e.g. collagen in tendons and ligaments, keratin in
hair and nail
6. Storage proteins
e.g. store amino acids; ovalbumin in egg white

7. Contractile proteins
form structures that create movements
e.g. actin fibres in muscles
8. Transport proteins
transport things around body or across membranes
e.g. haemoglobin carries O2 from lung to other body parts
 Binding and catalysis
Ligand binding is central to the many biological roles of proteins.

Specificity comes from a binding pocket that is complementary in

size, shape and electrostatic potential surface to the target.

Antibodies bind to foreign ligands to recognise invaders and

tag them for destruction by the immune system

Enzymes, protein catalysts, bind their substrates and products

and accelerate reactions by stabilizing transition states.
04_30_selective binding.jpg
04_31_specific ligands.jpg
 Antibodies
• One function of proteins is to recognise and bind to specific target
molecules - small organic molecules or other macromolecules.

• Antibodies are immune system proteins (immunoglobulins). Each

antibody consists of four polypeptides– two heavy chains and two light
chains joined to form a "Y" shaped molecule.

• They can bind to almost any molecule by adapting the composition of

the variable chains to produce a suitable binding pocket.

• Recognition is achieved by setting up a binding pocket that is

complementary in size, shape and electrostatic potential surface to the
target.
 Enzymes

Almost all cellular reactions are controlled by enzymes.

Enzymes function as catalysts, which are substances that speed up

reactions without being transformed in the reaction.

They increase the rate of reactions by a factor of between 106 to 1012 times
allowing the chemical reactions that make life possible to take place at
normal temperatures.

They are used over and over and a single enzyme molecule may mediate
thousands of reactions in a single second.
 Enzymes

Free energy

Reaction progress
 Enzymes

Free energy
How fast does A go to B?

How much A goes to B? B

Reaction progress
 Enzymes

Free energy
How fast does A go to B?
With enzyme the
A reaction is faster but the
endpoint is the same.

How much A goes to B? B

Reaction progress
 Enzymes

Free energy
How fast does A go to B?

A With enzyme

How much A goes to B? B

Reaction progress
Enzymes accelerate reactions by stabilising (binding) transition states.
They do not change equilibrium constants.
Types of enzymes-there is international classification of enzymes,
based on the reactions they catalyse.
Class Type of reaction catalysed
Oxidoreductases Oxidation-reduction. A hydrogen or electron donor
is one of the substrates
Transferases Chemical group transfer of the general form
A-X + B to A + B-X
Hydrolases Hydrolytic cleavage of C-C, C-N, C-O and other
bonds (transfer of functional groups to water)
Lyases Cleavage (not hydrolytic) of C-C, C-N, C-O, and
other bonds, leaving double bonds; alternatively,
addition of groups to a double bond
Isomerases Transfer of groups within molecules to yield
isomeric forms (i.e change of geometrical
arrangement of a molecule)
Ligases Formation of C–C, C–S, C–O, and C–N bonds
by condensation reactions coupled to ATP
cleavage
Machines
Machines; walking along microtubules

Kinesin
Machines; walking along microtubules

Kinesin
 DTC students

• Fersht, A. Enzyme structure and mechanism

• Creighton, T.E. Proteins, structures and
molecular properties