lecture 8 - the amino acids i _ structure and chemical characteristics

8/18/2019 Lecture 8 - The Amino Acids I _ Structure and Chemical Characteristics

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The Amino Acids

I. Their Structure and Chemical Characteristics

The Lady of Shalott Waterhouse, John William 1888


2/27

Amino acids polymerize to form Proteins

• for the next several lectures we will examine the composition and structure ofproteins

• 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.


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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) sequence of amino acids

Secondary (2o

) discrete regions of higher order structure in polymerTertiary (3o) higher order folding of secondary structures

Quaternary (4o) 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.


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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

H2N – C – C

O

OHH

R

–

–

All possess:

-an α Carbon to which is attached

-an amino group

-a carboxylic acid group

-a hydrogen atom

-a unique sidechain (R)


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H2N – C – C

O

OHH

R

–

–

H2N – C – H

R

OHO

–

–C

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

is the

same as

or

H2N – C – C

O

OH

H

R

–

–


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H3N – C – CO

O-H

R–

–+

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:

(more on ionization of amino acids next class…)

The

zwitterionic form of

an amino acid


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Amino acids are chiral molecules

- non-superimposable mirror images

- only the L isomer is used for making proteins


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H3N – C – C

O

O-

H

R

–

–+

• 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

These 3 groups are

all polar


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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 byburying hydrophobic amino acids away from exposure to water molecules

Hydropathy Scale

-the relative hydrophobicityof amino acids H y d r o p h o b i c

H y d r o p h i l i c

note: most sources categorize

proline as more hydrophobic than

tyrosine and cysteine and these lattertwo as being somewhat hydrophilic.

Recall


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Hydrophobic Interactions

• Hydrophobic interactions occur between molecules that cannot interact with water.

•

Consider mixing oil and water. Oil molecules are called APOLAR because theycannot 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.


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Hydrophobic Side Chains

• either aliphatic or aromaticside chains

• remember, H2O can only interact

with ionic charges on molecules

or with other polar groups(dipoles, δ+/δ- 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


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A reminder about polarity and its consequences

and conversely, the meaning of :

apolar

or

non-polar

or

hydrophobic

(slides 12-16)


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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:

• 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)

δ- δ+

O H this separation of partialcharge is called a DIPOLE


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• Hydrogen bonding involves a DONOR where the H atom has partial

+ charge and an electronegative ACCEPTOR group

δ- δ+

donor acceptor

dashed yellow lineis the hydrogen bond

δ-


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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

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16/27

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.

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17/27

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 permanentdipole 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.


18/27

Hydrophobic Side Chains

• either aliphatic or aromaticside chains

• remember, H2O can only interact

with ionic charges on molecules

or with other polar groups(dipoles, δ+/δ- 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


19/27


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 groupsThe amide functional groups on Asn and Gln are also very polar.

Th A i A i id


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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?



21/27


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 groupsThe amide functional groups on Asn and Gln are also very polar.


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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?


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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

the imidazole ring of Histidine

both forms are abundant at physiological

pH making this amino acidchemically versatile

pka = 6


24/27

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


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carboxylate group

carboxyamide group

Seven amino acids have ionizable side chains


26/27

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

G l C t b t Sid Ch i Ch t i ti


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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-reactive…they 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 (δ+ or δ-) associated with them)

• polar side chains interact with H2O molecules either because of ionic charge orpartial 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.

lecture 8 - the amino acids i _ structure and chemical characteristics

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