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
 Partly soluble 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
 nature usually produces the
L amino acid

H
R C COOH

NH2
 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 NH3+ are

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 COO- R C 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-
NH3+ R C 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-

NH3+
 Cysteine
 The AA Cysteine exists as a dimer:
H
[O]
2 HS CH2 C COOH
[H]
NH2
H H
cysteine
HCOO C CH2 S S CH2 C COOH
NH2 NH2
cystine

a disulfide linkage
 Peptides

 AA are also called peptides

 They can be combined to form peptide bonds

H O CH 3 O
-H2 O
H2N CH C OH + H2 N CH C OH
glycine alanine
 Peptides

 Dipeptides

H O CH 3 O
-H2 O
H2N CH C OH + H2 N CH C OH
glycine alanine
H O CH3 O
H2 N CH C NH CH C OH

a peptide bond
 H O CH3 O
H2 N CH C NH CH C OH
amine a peptide bond acid
end 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 OH
alanylglycine
 Peptides
 Synthesis of Alanylglycine

CH3 O H O
-H2O
H2N CH C OH + H2N CH C OH
alanine glycine

CH3 O H O
H2N 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 5 AA 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 protein!) AA’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 CH2 C COOH HCOO C CH2 S S CH2 C COOH
[H]
NH2 NH2 NH2
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 of a protein is said to “denature” it
 Examples:
 Heat (boil an egg) to gelatin
 Addition of 6M Urea (breaks H bonds)
 Detergents (surface-active agents)
 Reducing agents (break -S-S- bonds)
 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