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Slide 1
 Amino acids –
R group properties
Module 3: Basics of protein building

Dr. Katrina Binger

Department of Biochemistry and Genetics Slide 2

Intended Learning Outcomes
(ILOs)
After this lesson students will be able to:
• Recall the single- and three-letter code of all 20
amino acids
• Classify amino acids based on their R-group
chemical properties
• Explain the significance of R-group properties on
amino acid interactions
• Compare and contrast the effect of silent, missense
and conservative point mutations on the amino acid
sequence and thereby protein structure

Slide 3
The 20 amino acids

Amino acids are known by their:

• Full name
• 3-letter abbreviation
• Single letter code
Slide 4
The R-group defines an amino acid’s
chemical properties

Remember, only the R-group

differs between amino acids;
the backbone is identical
Slide 5
General classification:
Hydrophilic vs. Hydrophobic

Hydrophilic:
water lovers

Hydrophobic:
water haters

Slide 6
R-group classifications: Aromatics

• Hydrophobic, big bulky

side chains have a steric
effect on protein structure
• Rings (Trp & Tyr) absorb
at 280 nm and used to
detect protein.

Slide 7
R-group classifications: Sulfurs

• Cysteine contains highly

reactive sulfur group
• Two cysteines can be
covalently joined together
by a disulphide bond
• Disulphide bonds can
form within a polypeptide,
or between different
polypeptides, e.g. insulin

Slide 8
R-group classifications: Charged

• Lys & Arg are normally positively

charged (pKa discussed next lecture)
• Nitrogen atoms are willing H acceptor;
therefore acts as a base (acid/base
properties discussed next lecture)
• Positive is attracted to negative: thus
form electrostatic/ionic interaction with
negatively charged amino acids

Slide 9
R-group classifications: Charged

• Asp & Glu are normally negatively

charged (pKa discussed next lecture)
• COOH group is a willing H donor;
therefore acts as an acid (acid/base
properties discussed next lecture)
• Positive is attracted to negative: thus
form electrostatic/ionic interaction with
positively charged amino acids

Slide 10
R-group classifications: Hydroxyls

• Enzymes known as kinases can

transfer phosphate [PO4]3- groups to
the oxygen of Ser and Thr
• This is called phosphorylation and
plays an important role in cellular
function, particularly signalling

Slide 11
R-group classifications: NH2 (amine)

• Amines love to form hydrogen bonds,

e.g. with water; which is why they are
usually on the surface of proteins

Slide 12
R-group classifications: CH3 (alkyl)

• Alkyl = contains carbon

and hydrogen
• AVIL: increasing size
and combination of alkyl
groups; resulting in
different sizes and
shapes, all of which are
hydrophobic

Slide 13
Hard to classify

Gives flexibility Rigid Positive/Negative

charged (discussed
next lecture)
Slide 14
What impact do amino acid side
chains have on protein function?

Slide 15
R-group interactions have a
critical impact on protein folding
The folding and 3D shape of a protein is due to chemical
interactions between amino acid R-groups.

These interactions can be:

• Hydrophilic (love H2O) vs. hydrophobic (hate H2O)
• van der Waals (between hydrophobic side chains)
• Disulfide bonds (between sulfur groups)
• Ionic or salt bridges (between positive & negative charges)
• Hydrogen bonds (between H2O)

Slide 16
What impact do amino acid side
chains have on protein function?
e.g. MKAWE

Slide 17
Side chains dictate a proteins
overall 3D shape = function

For example:
• Form active site of an
enzyme or receptor
• Can be targeted for
drug design

Slide 18
Interactions between side chains
dictate protein folding = function

• Hydrophilic = stay on the surface

• Hydrophobic = buried; form van
der Waals interactions
• Cysteines = form disulfide bonds
with other cysteines
• Ionic interactions or salt bridges
form between charged side chains
• Hydrogen bonds form between
other side chains or H2O

Slide 19
Point mutations can significantly
alter amino acid sequence

• In this example, G>C nucleotide

mutation changes the side chain from
a Tryptophan (bulky) to Cysteine (now
potential to form disulphide)
• This is also known as a missense
mutation

Slide 20
Point mutations can be silent

• Alternatively, because the genetic

code is degenerate, a point mutation
can be silent: giving rise to the same
amino acid

Slide 21
Mutations can have only a small impact if the
substitution is for the same class of amino acid

• If the mutation results in an amino acid

in the same class (e.g. aromatic,
hydroxyl, charged) this often has only
little impact on the protein’s function
and is called a conservative mutation

Slide 22
Summary

• The R-group or side chain of an amino acid is what gives

it its unique chemical property
• Amino acids can be classified into groups based on
similarities between their R-groups: presence of aromatic
rings; sulfur, oxygen or nitrogen atoms; positive or
negative charge
• Interactions between R-groups drives protein folding and
gives the protein its ultimate 3D shape and function
• Nucleotide point mutations can either drastically alter the
chemical property of side chains, or have little to no effect

Slide 23
Resources

• Lehninger Principles of Biochemistry Seventh

Edition (2017), W. H. Freeman and Company
• Chapter 3.1, 3.2

Slide 24