Amino Acids
and Proteins
• Proteins are composed of amino acids.
• There are 20 amino acids commonly
found in proteins. All have:
H
NH2
Cα COOH
R
Amino acids at neutral pH are dipolar ions
(zwitterions) because their α-carboxyl and
α-amino groups are ionized.
H
+
NH3
C
R
COO
Titration curve for Glycine:
pK22
8
pH
NH3+=
NH2
6
pK11
4
COOH=
COO-
2
0. 5 [NaOH]
Structure of glycine at differing pH values:
H
+
NH3
C
H
+
NH3
COOH
H
C
H
pH=1
pH=7
H
NH2
C
COO
H
pH=11
COO
pK22
8
6
pH
4
2
NH3+
pK11
COOH
Isoelectric
point (no net
charge)
0. 5 [NaOH]
Aliphatic Non-Polar Amino Acids
COO
COO-
-
H N
C
H CH2
H 2C
CH2
+
2
H3+N - C - H
CH3
alanine
proline
COO
COO-
-
H3+N - C - H
H3+N - C - H
CH
CH3 CH3
valine
COO-
COOH3+N - C - H
H3+N - C - H
CH2
CH2
H - C - CH3
CH
CH3 CH3
CH2
S
CH3
CH3
leucine
isoleucine
methionine
CH2
Aromatic Non-Polar Amino Acids
COO-
COO-
H3+N - C - H
H3+N - C - H
CH2
phenylalanine
CH2
C
CH
N
H
tryptophan
Polar Uncharged Amino Acids
COO-
COO-
COO-
H3+N - C - H
H3+N - C - H
H3+N - C - H
H
glycine
COOH3+N - C - H
CH2
CH2OH
serine
pKa=13
COOH3+N - C - H
CH2
SH
OH
tyrosine
cysteine
pKa=10.1
pKa=8.3
CHOH
CH3
threonine
pKa=13
Serine and Threonine can be PHOSPHORYLATED:
COO-
ATP
ADP, Pi
H3+N - C - H
H3+N - C - H
CH2OPO32-
CH2OH
serine
serine
COOH3+N - C - H
COO-
ATP
ADP, Pi
COOH3+N - C -
H
CHOH
CHOPO32-
CH3
CH3
threonine
threonine
Disulfide Bond:Two cysteine
COOH3+N - C - H
CH2
S
S
CH2
H3+N - C - H
COO-
residues condense. Disulfide
bonds may occur between
cyteine residues within the
same protein (intrachain) or
between two cystein residues
occuring in different proteins
(interchain). Disulfide
formation is a major factor in
the determination of protein
structure.
Permanent waving is the result
of the reduction of disulfides in
the α-keratin protein (that hair is
made of) and spontaneous
re-oxidation of those disulfide
bonds in air.
Polar Uncharged Amino Acids
COO-
COO-
H3+N - C - H
H3+N - C - H
O
CH2
CH2
C
CH2
C
NH2
asparagine
O
NH2
glutamine
Acidic Amino Acids
COO-
COO-
H3+N - C - H
H3+N - C - H
O
CH2
CH2
C
CH2
O-
aspartate
C
O
O-
glutamate
pKa=3.9
pKa=4.3
Basic Amino Acids
COO-
COO-
COO-
H3+N - C - H
H3+N - C - H
H3+N - C - H
CH2
CH2
CH2
CH2
NH3+
Lysine
CH2
CH2
CH2
NH
C
H2+N
NH2
arginine
pKa=10.5
pKa=12.5
CH2
HC=
HC C
N
NH
C
H
histidine
pKa=6.0
Chirality in Amino Acids
CHO
HO - C - H
CH2OH
L-Glyceraldehyde
COOH
H3+N - C - H
CHO
H - C - OH
CH2OH
D-Glyceraldehyde
COOH
H - C - NH3+
CH3
CH3
L-Alanine
D-Alanine
L amino acids occur in proteins!
The Peptide Bond
• Bond occurs between the α-amino
group of one amino acid and the
α-carboxyl group of another amino
acid
• A condensation reaction where
the elements of H20 are removed
H O
NH2 - C - C - OH
H
H
H N - C - COOH
H H
H O
H
NH2 - C - C - OH H - N - C - COOH
H
H H
H O
H
NH2 - C - C - OH H - N - C - COOH
H
H H
H O
H
NH2 - C - C
N - C - COOH
The Peptide Bond!!
H
H O
H H
H
NH2 - C - C N - C - COOH
H
H H
Functions of Proteins:
• Enzymes
• Regulatory Proteins
• Structural
• Transport
• Storage
• Contractile
Three Classes Based on Shape
and solubility:
• Fibrous (collagen)
• Globular (enzymes)
• Membrane (CP 43)
Conjugated Proteins:
• Prosthetic groups: non-amino acid
components
• Coenzyme: organic molecules (vitamins)
involved in catalysis
• Metalloproteins
• Glycoproteins
• Lipoproteins
• Nucleoproteins
• Phosphoproteins
• Protein chains have a direction.
• By convention the N-terminus is taken to
be the beginning of a polypeptide chain.
H O
H O
H
NH2 - C - C - N - C - C -N - C - COOH
H H
H
H CH3
Glycine-Glycine-Alanine
Protein Architecture
• Conformation:
Conformation The spatial arrangement
of atoms in a protein.
• There are 4 levels of organization:
1) Primary Structure: linear sequence
of amino acids in a polypeptide.
2) Secondary Structure: local conformation
of the peptide backbone.
The Peptide Bond is a Resonance Structure:
H O
H
NH2 - C - C N - C - COOH
H
H O-
H H
H
NH2 - C - C N+ - C - COOH
H
H H
Peptide bonds are
resonance
structures and
cannot freely
rotate
Rotation occurs
only about the
N-Ca (phi; φ ) and
C-Ca (psi; ψ) bonds
Each carboxyl oxygen is
hydrogen bonded to the
amino group of the amino
acid four residues above
Single turn =
0.56 nm = 3.6
amino acids
Stretches of + and - charged
amino acids destabilize; proline
destabilizes; amino acids with
bulky R groups destabilize;
polyleucine and polyalanine are
good helix formers.
α-Helix
C
N
Parallel;
5 sheets
or more
β-pleated
sheet
C
N
N
C
C
N
Anti-Parallel: 2 or
more sheets; silk
is an example
Glycine and
Alanine often
found in β-sheets
Composed of 4
amino acids;
the first is
hydrogen
bonded to the
fourth
β-Bend
Glycine (small and
flexible) and proline
(kinks) occur in
β-bends
• Secondary structures are arranged into
domains or modules.
3) Tertiary Structure: the way in which the
secondary structural elements are
folded; the spatial distribution of side
chains.
• Hydrophobic effect is a major factor in
determining the folding pattern
• Secondary structural elements fold first to
maximize H-bonds; then interactions
between these elements occur
4) Quaternary Structure: subunit
organization; kinds of subunits, number
of subunits and the ways in which they
interact with one another.
• Multisubunit proteins are also referred to as
oligomers.
• Proteins composed of a single type of
monomer are homomultimeric; those
composed of two or more different subunits
are heteromultimeric.
• Hemoglobin has two each of two different
subunits; it’s structure is designated α2β2.
Forces Driving Quaternary Association:
Hydrogen Bonding
Electrostatic Interactions
Van Der Waals Interactions
Hydrophobic Interactions
Structure determines function: one way to study
this relationship is to alter the structure and
determine its effect on function.
Protein Denaturation: Loss of tertiary and
quaternary structure (sometimes 2o structure).
β-mercaptoethanol: disulfide reducing agent
SDS: detergent; disrupts hydrophobic core
urea: disrupts hydrogen bonds
water: disrupts electrostatic interactions
organic solvents: disrupts interactions of
hydrophobic residues
temperature: complete denaturation