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The Amino Acids

I. Their Structure and Chemical Characteristics

The Lady of Shalott

Waterhouse, John William 1888

Amino acids polymerize to form Proteins


for the next several lectures we will examine the composition and structure of
proteins
proteins are the most important group of molecules in biological systems
because many of them are enzymes (catalysts that permit the chemistry
of life under the moderate conditions that permit cellular life).
DNA is a relatively inert carrier of information mostly in the form of genes
that are the codes for making proteins.
DNA RNA Protein
proteins themselves are required for the act of transcription and translation to
produce the thousands of different proteins required for life.

Four levels of Protein Structure


amino acids polymerize to form proteins

the order (sequence) of amino acids in a protein, which is specified by the order
(sequence) of nucleotides in a gene, is called its primary structure.
Primary (1o)
Secondary (2o)
Tertiary (3o)
Quaternary (4o)

sequence of amino acids


discrete regions of higher order structure in polymer
higher order folding of secondary structures
multi-protein (subunit) assemblies

Today we will examine the monomeric constituents of proteins (the amino acids)
an important concept is that with respect to the fully folded and active protein,
everything depends upon the primary sequence of the amino acids in
the protein
Later we will examine the 1o, 2o, 3o, 4o structure of proteins.

The Amino Acids


organic molecules containing an amino group and a carboxylic acid (carboxylate)
group

at least 500 amino acid species exist in nature


at least 200 of these are found in biological entities

just 20 of these (+ 3 rare amino acids) are used to build proteins


All possess:

H2N C C
OH
H

-an Carbon to which is attached


-an amino group
-a carboxylic acid group
-a hydrogen atom
-a unique sidechain (R)

Note that the structure of amino acids can be depicted in various ways

HO

H2N C C
OH
H

is the
same as

H2N C H
R

or

H2N C C
R

OH

The amino and carboxyl group can be ionized depending on the surrounding pH.

At the pH typical of cytoplasm (pH 6.8 7.4, physiological pH) the amino group will be
protonated and the carboxyl group will be deprotonated.
Thus we typically draw amino acids in this form:

H3N C C
O
H

The
zwitterionic form of
an amino acid

(more on ionization of amino acids next class)

Amino acids are chiral molecules

- non-superimposable mirror images


- only the L isomer is used for making proteins

The side chain (or R group) for each amino acid is unique
Imparts unique chemical character to each amino acid
Amino acids are therefore largely defined by the side chain
Major side chain characteristics:
Apolar (or non-polar or hydrophobic)
Polar and (or hydrophilic) (but uncharged)
Negatively charged (Acidic) - full ionic negative charge
Positively charged (Basic) - full ionic positive charge

H3N C C
O
H

These 3 groups are


all polar

A survey of the side chains of the 20 common amino acids


first, the amino acids with apolar (hydrophobic) sidechains
when we talk about protein folding into their 3-dimensional shapes later, it
will become apparent that protein folding patterns are partially driven by
burying hydrophobic amino acids away from exposure to water molecules

Hydrophobic

Hydropathy Scale
-the relative hydrophobicity
of amino acids

Hydrophilic

note: most sources categorize


proline as more hydrophobic than
tyrosine and cysteine and these latter
two as being somewhat hydrophilic.

Recall

Hydrophobic Interactions
Hydrophobic interactions occur between molecules that cannot interact with water.
Consider mixing oil and water. Oil molecules are called APOLAR because they
cannot interact with water (through Hydrogen bonding).
They therefore coalesce together (interacting with each other through
Van der Waals forces) and in doing so minimize their surface area contact
with water molecules.

Hydrophobic interactions (should really be called the Hydrophobic Effect) are


very important to structure of DNA and proteins and membranes in cells.

Hydrophobic Side Chains


either aliphatic or aromatic
side chains
remember, H2O can only interact
with ionic charges on molecules
or with other polar groups
(dipoles, +/- partial charges)
this is why, in a fully folded protein,
these amino acids are usually
buried internally.
note that the larger the hydrocarbon
group the more hydrophobic

A reminder about polarity and its consequences


and conversely, the meaning of :
apolar
or
non-polar

or
hydrophobic

(slides 12-16)

Hydrogen Bonds
A functional group can become a Hydrogen bond donor whenever an H atom is
covalently bonded to an atom that is very electronegative (such as N or O)
because the H atom takes on a partial + charge, as shown below:

this separation of partial


charge is called a DIPOLE

an unequal sharing of electrons: electrons spend more time around


the strongly electronegative Oxygen making it more negative and the
hydrogen more positive (i.e. polar covalent bond)

Hydrogen bonding involves a DONOR where the H atom has partial


+ charge and an electronegative ACCEPTOR group

dashed yellow line


is the hydrogen bond

donor

acceptor

Water can also dissolve other molecules that are not ionic so long as they are also polar
(e.g. like sugar molecules)
by forming Hydrogen bonds with the molecules.

sucrose
glucose and fructose disaccharide

Hydrophobic molecules (such as oils) cannot dissolve in water because oils are
neither ionic or polar and water molecules therefore cannot electrostatically
interact with them.

Three types of Van der Waals Interactions


1. Dipole-dipole. Occur between
molecules containing permanent dipoles.
Hydrogen bonds are a special type of this
interaction.

2. Dipole - induced dipole. A permanent


dipole in one molecules induces dipole in
another resulting in attractive force.

3. Induced dipole-induced dipole. Random


fluctuations in electron distribution in one
molecule sets up temporary dipole. This induces
dipole in adjacent molecule, resulting in
interaction. Weak but very important to the
cohesiveness of everything.

Hydrophobic Side Chains


either aliphatic or aromatic
side chains
remember, H2O can only interact
with ionic charges on molecules
or with other polar groups
(dipoles, +/- partial charges)
this is why, in a fully folded protein,
these amino acids are usually
buried internally.
note that the larger the hydrocarbon
group the more hydrophobic

Polar (Hydrophilic) Side Chains


just as we discovered that attaching a polar group (e.g OH group) to a hydrocarbon
like hexane markedly increases its solubility in water, so is the case with amino acids.
Ser, Thr, Tyr all have OH groups
The amide functional groups on Asn and Gln are also very polar.

The Aromatic Amino acids


- two are non-polar (Trp and Phe) and one is polar (Tyr) because of the alcohol group
- phenylalanine is just an alanine with a benzene (phenyl) ring attached
- tyrosine is just phenylalanine with an alcohol group
- tryptophan has a double ring (6 carbon benzene ring fused to a 5 carbon pyrolle ring)
(indole group)

tryptophan is usually considered quite apolar/hydrophobic but it is actually more polar


than phenylalanine - why?

Polar (Hydrophilic) Side Chains


just as we discovered that attaching a polar group (e.g OH group) to a hydrocarbon
like hexane markedly increases its solubility in water, so is the case with amino acids.
Ser, Thr, Tyr all have OH groups
The amide functional groups on Asn and Gln are also very polar.

Both serine and threonine are polar because they have polar OH groups
One of these is more polar/hydrophilic than the other. Which one is the most polar
amino acid and why?

Positively Charged Side Chains


these are positively charged at
physiological pH and are called
basic amino acids.
they are charged, therefore polar
(hydrophilic) and usually exposed
on the surface of proteins
pka = 6
the imidazole ring of Histidine

both forms are abundant at physiological


pH making this amino acid
chemically versatile

Negatively Charged Side Chains


these are negatively charged at
physiological pH and are called
acidic amino acids.
they are charged, therefore polar
(hydrophilic) and usually exposed
on the surface of proteins
note that both have carboxylic acid
functional groups on side chains

carboxylate group

carboxyamide group

Seven amino acids have ionizable side chains

these are the amino acids with important roles in the active site
some play a direct role in catalysis and these are called CATALYTIC amino acids
others play an accessory role (eg. substrate/TS binding, other interactions) and
are just called active site amino acids

General Comments about Side Chain Characteristics


the side chains of hydrophobic amino acids are neither polar nor charged,
therefore water molecules cannot interact with them
hydrophobic side chains are usually non-reactivethey do not interact with other
groups (except through van der Waals interactions) and they do not engage in
chemical reactions (electron transfer events)
all charged side chains are polar because of the ionic charge
but not all polar side chains are charged (though they will have dipoles (partial
charges (+ or -) associated with them)
polar side chains interact with H2O molecules either because of ionic charge or
partial charges and they are likely to be much more chemically reactive
(engage in bond making or breaking reactions via transfer of electrons).
in a fully folded protein, hydrophobic amino acids are usually buried in the interior
whereas hydrophilic amino acids are on the surface of the protein.