Proteins

Proteins
(Greek = “of first importance”)

Functions:
 Structure - skin, bones, hair, fingernails

 Catalysis - biological catalysts are enzymes

 Movement - muscle: actin and myosin

 Transport - hemoglobin, transport thru membranes
 Proteins
Functions:
 Hormones - insulin, oxytocin, HGH, etc.

 Protection - antigen-antibody reactions,

fibrinogen in clotting
 Storage - casein in milk, ovalbumin in eggs, ferritin in
liver-stores iron
 Regulation - control in expression of genes
 Proteins
Protein types:
 9000 different proteins in a cell
 Individual human being >100,000 different

 Fibrous Protein
 Insoluble
in H2O
 Used mainly for structural purposes

 Globular Protein
 Partlysoluble in H2O
 Usually not used for structural purposes
 Proteins are Natural Polymers

 Proteins are constructed in the body from many repeating

units call amino acids

 Just like other polymers the amino acids (monomers) are

joined together to make long chains (polymers) – but we
call them proteins instead

 All of the polymer information applies to proteins – cross

linking, rings, polarity etc.
 Amino Acids
The Building Blocks of proteins
 Contains an amino group and an acid group
 Nature synthesizes about 20 common AA
 All but one (proline) fit this formula:

 AA Proline:
H
R C COOH
COOH
NH2
N
H
proline
 Amino Acids
Amino Acids (AA)
 The twenty common are Called alpha amino acids
 One and three letter codes given to 20 common AA
 All but glycine (where R=H)
exist as a pair of enantiomers
 natureusually produces the
L amino acid

H
R

C
 Amino Acids

 Amino Acids (AA)

 Sometimes classified
as AA with:
nonpolar R groups
 polar but neutral
R groups
acidic R groups
 basic R groups
 Zwitterions

 An acid -COOH and

an amine -NH2 group
cannot coexist

 The H+ migrates to
the
-NH2 group
 COO- and NH + are
3
actually present, called
a “Zwitterion”
 Zwitterions

 Zwitterion = compound where both a positive charge

and a negative charge exist on the same molecule

 AA are ionic compounds

 They are internal salts

 In solution their form changes

depending on the pH
 Zwitterions

pH = 1-5 pH = 10-14

more acidic more basic

excess H+ excess OH-

H H H
R C COOH R C R C COO-
COO-
NH3 + NH3 + NH2
 Zwitterions

pH = 1-5 pH = 10-14

more acidic more basic

excess H+ at pI excess OH-

(isoelectric
point) H
H
charge = 0
R C COOH H R C COO-
R C
NH3 +
COO- NH2
NH3 +
 pI
The pI is the “isoelectric point”
The pI is the pH where
NO charge is on the AA:

at pI
charge = 0
(Not necessarily H
at a neutral pH) R C
COO-

NH 3 +
 Cysteine
The AA Cysteine exists as a dimer:
H
[O]
2 HS CH2
C [H]
COOH H
H
HCOO COOH
NH2
C CH 2 S S CH2
cysteine C NH2
cystin
NH2 e
a disulfide linkage
 Peptides

AA are also called peptides

They can be combined to form peptide bonds

H O CH3
-H2 O
H2 N CH C OH + 2
glycine O
H N CH C OH
alanine
 Peptides

Dipeptide
s

H O CH3
-H2 O
H2 N CH C OH + 2
glycine O
H N
H CH O C OH CH 3 O
alanine NH CH C OH
H2 N CH C

a peptide bond
 H O CH3 O
H2 N NH CH C OH
CH C a peptide bond acid
end
amine
end

glycylalanine (Gly-Ala), a dipeptide

 Peptides
Glycylalanine is not the same as Alanylglycine

H O CH3 O
H2 N CH C NH CH C OH
glycylalanine

CH3 O H O

H2 N CH C NH CH C
alanylglycine
OH
 Peptides
Synthesis of Alanylglycine

CH3 O H
-H 2O
H2N O
CH C OH + H2N CH C OH
alanine glycin
e

CH3 O H O

H2 N CH C NH CH C
OH
alanylglycine
 Peptides
Addition of peptides (head to tail)
 Formation of:
dipeptides
tripeptides
tetrapeptides
pentapeptides
polypeptides
PROTEINS

AA’
s
 Proteins
 Proteins usually contain about 30+ AA
 AA known as residues
 One letter abbreviations
 G, A, V, L
 Three letter abbreviations

 Gly, Ala, Val, Leu

 N terminal AA (amine end) on LEFT
 C terminal AA (carboxyl end) on RIGHT
glycylalanine Gly-Ala
G-A
 Polypeptides

side chains
Polypeptides

R R R R R R
N CH C N CH C N CH C N CH C N CH C N CH C
H O H O H O H O H O H O

amino acid
residues
peptide bonds peptide bonds
 Solubility

 Polypeptides or Proteins
 If there is a charge on a polypeptide, it is more soluble
in aqueous solution
 If there is NO CHARGE (neutral at pI), it is LEAST
SOLUBLE in solution

H H
R C COOH R C COO-

NH3+ NH2
charged charged
 Protein Structure

Primary Structure
1o
 Linear sequence of AA

Secondary Structure
2o
 Repeating patterns ( helix,  pleated sheet)

Tertiary Structure
3o
 Overall conformation of protein

Quaternary Structure 4o
 Multichained protein structure
 Protein Structure
Primary Structure
1o
 Linear sequence of AA
R R R R R R
N CH C N CH C N CH C N CH C N CH C N CH C
H O H O H O H O H O H O

AA 1 AA 2 AA 3 AA 4 AA AA
5 6
With any 6 AA residues,
the number of possible combinations is
6 x 6 x 6 x 6 x 6 x 6 = 46656
AA’
s
 Protein Structure
Primary Structure
R R R R R R
N CH C N CH C N CH C N CH C N CH C N CH C
H O H O H O H O H O H O

AA 1 AA 2 AA 3 AA 4 AA 5 AA
6

With any 6 of the 20 common AA residues,

the number of possible combinations is
20 x 20 x 20 x 20 x 20 x 20 = 64,000,000
(and this is not nearly large enough to be a AA’
protein!) s
 Protein Structure
Primary Structure
 A typical protein could have 60 AA residues. This would
have 2060 possible primary sequences.
2060 = 1078
This results in more possibilities for this small protein
than there are atoms in the universe!
 Protein Structure

 Primary Structure
 Sometimes small changes in the 1o
structure do not alter the biological
function, sometimes they do.

AA’
s
 Changes and Effect of AA change

Sickle cell anemia – only one change in an amino

acid – changes the hemoglobin
 Protein Structure

 Secondary Structure
 Repeating patterns
within a region
 Common patterns
 helix
 pleated sheet
 Originally
proposed by
Linus Pauling
Robert Corey

AA’
s
 Protein Structure

Secondary Structure

 helix
 Single protein chain
 Shape maintained by
intramolecular H bonding
between -C=O and H-N-
 Helical shape
 helix is clockwise
 Protein Structure
Secondary Structure
 pleated sheet
 Several protein chains
 Shape maintained by
intramolecular H bonding
and other attractive
forces between chains
 Chains run anti-parallel
and make U turns at ends
 Protein Structure

Secondary Structure
Random Coils
 Few proteins have
exclusively  helix or
 pleated sheet
 Many have non-repeating
sections called:
Random Coils
 Collagen Protein Structure

Secondary Structure
Triple Helix of Collagen
 Structural protein of
connective tissues
 bone, cartilage,
tendon
 aorta, skin
 About 30% of
human
body’s protein
 Triple helix units =
tropocollagen
 Tertiary Structure

 The Three dimensional arrangement of every atom in

the molecule
 Includes not just the peptide backbone but the side
chains as well
 These interactions are responsible for the overall
folding of the protein
 This folding defies its function
and it’s reactivity
 Tertiary Structure

The Tertiary structure is formed by the following

interactions:
Covalent Bonds
Hydrogen Bonding
Salt Bridges
Hydrophobic Interactions
Metal Ion Coordination
Tertiary Structure –Covalent Bonding
 The most common covalent bond in forming the
tertiary structure is the disufide bond
 It is formed from the disulfide
interaction of cysteine

H H H
[O]
2 HS CH 2 C HCOO C CH 2 S S CH 2 C COOH
[H]
COOH
NH 2 NH 2 NH 2
cysteine cystine
Tertiary Structure –Hydrogen Bonding

Anytime you have a hydrogen connected to a F O

of N – you can get hydrogen bonding
These interactions can occur on the side chain,
backbone or both
 Tertiary Structure –Salt Bridge

 Salt bridges are due to charged portions of the protein.

 Opposite charges will attract and form ionic bonds
 Some examples are the NH3+ and COO- areas of the
protein
Tertiary Structure –hydrophobic interactions

 Because the nonopolar groups will turn away from the

water and the polar groups toward it, hydrophobic
interactions take place.
 These interactions are strong enough to help define
the overall structure of a protein
Tertiary Structure –Metal Ion Coordination

 Two side chains with the same charge would normally

repel each other
 However, if a metal is placed between them, they will
coordinate to the meal and be connected together.
 These metal coordinations are important in tertiary
structure formation
Tertiary Structure
 Quaternary Structure

 Highest level of organization

 Determines how
sub unit fit together
 Example Hemoglobin
(4 sub chains)
2 chains 141 AA
 2 chains 146 AA

- Example -
Collagen
 Denaturation
Denaturation
 Any physical or chemical agent that destroys
the
 conformation
Examples: of a protein is said to “denature” it
 Heat (boil an egg) to gelatin
 Addition of 6M Urea (breaks H bonds)
 Detergents (surface-active agents)
 Reducing agents -S-S- bonds)
(break
 Denaturation

 Denaturation
 Examples:
Acids/Bases/Salts (affect salt bridges)
Heavy metal ions (Hg2+, Pb2+)
 Some denaturation is reversible

 Urea (6M) then add to H2O

 Some is irreversible

Hard boiling an egg

 Denaturation

Denaturation