Download IV. -Amino Acids: carboxyl and amino groups bonded to

IV. -Amino Acids: carboxyl and amino groups bonded to -Carbo n
A. Acid/Base properties
1. carboxyl group is proton donor ! weak acid
2. amino group is proton acceptor ! weak base
3. At physiological pH: H3N+-C -C O O B. Ca is tetrahedral and bonded to 4 different groups
1. L configuration for all natural amino acids (few exceptions)
2. 20 different R groups
C. Classification based on R-group - know one example from each
1. Aliphatic-hydrophobic 2. A r o m a t i c - h y drophobic
3. Polar Uncharged-hydrophilic 4. A c i d i c-hydrophilic 5. B a s i c - hydrophilic
V. Polypeptides and Proteins
A. Peptide Bond
1. join amino group of one amino acid with carboxyl group of another by forming and
amide bond between them ! Peptide Bond
2. C-N bond has partial double bond character
B. Peptides and Polypeptides
1. Peptides contain relatively few amino acids linked by peptide bonds: dipeptide,
tripeptide, tetrapeptide, ….
2. Polypeptide contains many amino acids and if there are very many amino acids
one can call it protein
C. Proteins have molecular weights > several thousand and have 3-4 levels of
structure
1. Primary Structure (1°) sequence of amino acids connected by peptide bo n d s
2. Secondary Structure (2°) local conformation of peptide bond backbone stabilized
by H-bonds: -helix: intrachain H-bonds & -sheet: interchain H-bonds
3. Tertiary Structure (3°): The complete 3-dimensional structure described by the
way the polypeptide chain folds back on itself; stabilized by interactions (bonds)
between the amino acid R-groups. Hydrophobic Bonds & van der Walls
Interactions – most important
4. Quaternary Structure (4°): only some proteins have 4° structure which is the
association of more than one polypeptide
Complex Polymer
(Macromolecule)
Polysaccharide
(Complex Carbohydrate)
Monomer
Simple Polymer
Monosaccharide
(Sugar)
Oligosaccharide
Nucleotide
Oligonucleotide
Nucleic Acid
Peptid e
Polypeptide
Protein
Amino Acid
An Overview of Protein Functions
Table 5.1
Describing Macromolecular Structure
α carbon
α-Amino Acids
Amino group
Carboxyl group
pH ~7
at high pH
H
+1 Charge
- H+
+ H+
H
O
H 3N C C
OH
R
+
O
H 3N C C
O
R
+
0 Charge
- H+
+ H+
H
At low pH
O
H 2N C C
O
R
-1 Charge
Stereochemistry -- Tetrahedral α-Carbon
L-Alanine
O
O
O
N
C
D-Alanine
α-Carbon
C
C
C
C
C
O
N
20 Different Amino Acids Are Found in Proteins
1-Letter
Name
3-Letter
1-Letter
Name
3-Letter
A
Alanine
A
M
Methionine
Met
C
Cysteine
Cys
N
Asparagine
Asn
D
Aspartic Acid
Asp
P
Proline
Pro
E
Glutamic Acid
Glu
Q
Glutamine
Gln
F
Phenylalanine
Phe
R
Arginine
Arg
G
Glycine
G
S
Serine
Set
H
Histidine
H
T
Threonine
Thr
I
Isoleucine
Ile
V
Valine
Val
K
Lysine
Lys
W
Tryptophan
Trp
L
Leucine
Leu
Y
Tyrosine
Tyr
Fig. 5.16a: Non-polar, hydrophobic aliphatic and aromatic amino acids
often cluster together and are found in the interior of proteins
Nonpolar side chains; hydrophobic
Side chain
Glycine
(Gly or G)
Methionine
(Met or M)
Alanine
(Ala or A)
Valine
(Val or V)
Phenylalanine
(Phe or F)
Leucine
(Leu or L)
Tryptophan
(Trp or W)
Isoleucine
(Ile or I)
Proline
(Pro or P)
Fig. 5.16b: Polar
uncharged side chains; hydrophilic
Serine
(Ser or S)
Threonine
(Thr or T)
Cysteine
(Cys or C)
Tyrosine
(Tyr or Y)
Asparagine
(Asn or N)
Glutamine
(Gln or Q)
Fig. 5.16b: Amino Acids with Hydroxyl Groups in their Sidechains (S, T, Y)
These amino acids can also be modified by phosphorylation
(addition of phosphate to the hydroxyl group)
O-
Side chain-O-H
Side chain-O-P-OO
Fig. 5.16b: Amino Acids with Hydroxyl Groups in their Sidechains (S, T, Y)
O-PO3
O-PO3
These amino acids can also be modified by phosphorylation
(addition of phosphate to the hydroxyl group)
O-
Side chain-O-H
Side chain-O-P-OO
Aspartic acid Glutamic acid
(Glu or E)
(Asp or D)
Lysine
(Lys or K)
Arginine
(Arg or R)
Histidine
(His or H)
Note:
similar size and shape
but different
chemical properties
Asparagine (Asn) N
Aspartic Acid (Asp) D
Glutamine (Gln) Q
Glutamic Acid (Glu) E
Aromatic side chains (F,W,Y)
Tyrosine (Tyr) Y
Phenylalanine (Phe) F
Tryptophan (Trp) W
Ring system in side chain absorbs ultra-violet (UV) light
giving us a way of measuring protein concentration
Note similar size and shape of Tyr and Phe
(only difference is extra –OH group in Tyr making it
more hydrophilic)
Special cases:
Glycine is the smallest amino acid and its small
side chain can fit into small spaces in protein
Glycine (Gly) G
Cysteine (Cys) C
The sulfhydryl group (-S-H) of two
cysteines can react to form a covalent
disulfide bridge (-S-S-)
The side chain of proline is covalently
linked back to the α-amino group. This
limits the rotation of the side chain and
introduces kinks in proteins
Proline (Pro) P
Amino Acids Whose Structures You Need to Know
Alanine (Ala)
Aliphatic hydrophobic
Phenylalanine (Phe)
Aromatic hydrophobic
Serine (Ser)
Polar uncharged
Lysine (Lys)
Basic
Aspartic Acid (Asp)
Acidic
Fig. 5.17: Peptide Bonds Link Amino Acids
Peptide bond
New peptide
bond forming
Side
chains
Backbone
Amino end
(N-terminus)
Peptide
bond
Carboxyl end
(C-terminus)
Peptide Bond: How proteins (polypeptides) are made from amino acids?
H
H
O
N C C O
H
R 2
H
H
O
H 3N C C
OH
R 1
+
H
H 2O
O
O
H 3N C C N C C O
R1 H R2
+
Amide bond
Lone electron pair on
N forms second bond
O
C C N C
H
δ-
O
Cα C N δ+
Cα
H
O+
C C N C
H
or
O
C C N C
H
The Peptide Bond group is
Polar and Planar
(the atoms lie on a plane)
The π bond is shared between the O and N in
the Peptide Bond Group. Thus, each C=O and
C=N bond behaves like a double bond, and there
is no rotation around the bonds connecting these
atoms. Furthermore, all of the atoms of the
peptide bonding group lie on a plane.
Peptide Bond: Structural characteristics
Peptide Bonds
free rotation is not possible
around C-O and C-N bonds.
Rotation is possible around
the single bonds to the Cα’s
O
C
Cα
N
H
Cα
H
N
C
Cα
O
Planar Peptide Bond groups joined at Cα’s
Side Chain
Main
Chain
Amino Terminus
Carboxy Terminus
Aspartame a.k.a. NutraSweet - Is a Dipeptide
AspartylAlanineMethylEster,
a dipeptide. It is shown in two
orientations to demonstrate the
120° bond angles between
between the atoms of the peptide
bond, and the fact that all of these
atoms lie on a plane.
120°
Secondary Structure: Local folding of the polypeptide backbone
1.5 Å
Hydrogen
Bond
3.6 residues/turn
5.4 Å
.5 Å
Hydrogen
Bond
Fig. 5.18: Tertiary Structure
Describes overall fold of polypeptide backbone
β-sheet
α-helices
Folding puts some amino acid side chains
(Hydrophobic) in interior and some (Hydrophilic) on
exterior surface of protein
Different functional groups on surface give local
sites distinct shapes and specific properties
Fig. 5.20: What
Bonds Stabilize Tertiary Structure?
1.  Hydrophobic and van derWaals
Interactions: Packing (clustering) of
hydrophobic side chains into
interior away from water, keeping
most hydrophilic side chains on
surface.
2. Hydrogen bonds of secondary
structure elements
3. Ionic interactions between
oppositely charged side chains
4. Some proteins are also stabilized
by disulfide bonds between pairs
of cysteine side chains
Fig. 5.21: The
Four Levels of Protein Structure
Primary
Structure
Secondary
Structure
β pleated sheet
+H
3N
Amino end
Examples of
amino acid
subunits
α helix
Tertiary
Structure
Quaternary
Structure
Level of
Structure
Type of Bond
Between peptide
bond groups
Hydrophobic Bond most
important + others
Fig. 5.22: Changing A Proteins’s Amino Acid Sequence Can Change Its Shape
Sickle-cell hemoglobin
Normal hemoglobin
Primary
Structure
1
2
3
4
5
6
7
Secondary
and Tertiary
Structures
β subunit
Quaternary
Structure
Function
Normal
hemoglobin
Molecules do not
associate with one
another; each carries
oxygen.
α
Red Blood
Cell Shape
10 µm
β
α
β
1
2
3
4
5
6
7
Exposed
hydrophobic
region
Sickle-cell
hemoglobin
α
β subunit
Molecules crystallize
into a fiber; capacity
to carry oxygen is
reduced.
β
α
β
10 µm
Fig. 5.23: Amino Acid (primary structure) Sequence Determines Shape
increase temperature, change pH,
add chemical agents that
disrupt hydrogen bonds,
ionic bonds
and disulfide bridges
Anfinsen
experiment
(1965)
Denaturation
(Unfolding)
Folding
(spontaneous)
Normal protein
(Biologically active)
Renaturation
Denatured protein
(Biologically inactive)
Proteins Form a Variety of Shapes and Sizes
http://www.sci.sdsu.edu/TFrey/ProtStructClass/
Quaternary Structure: Some proteins form stable
oligomeric structures containing two or more polypeptides
Antibodies
Hemoglobin
Photosynthetic
Reaction Center
(membrane protein)
http://www.sci.sdsu.edu/TFrey/ProtStructClass/
Membrane Proteins: Some are a single polypeptide
others have Quaternary Structure
Bacteriorhodopsin
Photosynthetic
Reaction Center
Bacterial
Porin
(membrane protein)
http://www.sci.sdsu.edu/TFrey/ProtStructClass/
Cofactors: Some proteins bind ions and/or organic
molecules to help them fulfill their function
Hemoglobin
Myoglobin
http://www.sci.sdsu.edu/TFrey/ProtStructClass/
Molecules that interact stably have complementary shapes
(fit like a lock-and-key or a hand in a glove)
so that they can make lots of weak intermolecular bonds