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 -COO-

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. Aromat ic - 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 bonds

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

Monomer Simple Polymer Complex Polymer (Macromolecule)

Monosaccharide (Sugar)

Oligosaccharide Polysaccharide

(Complex Carbohydrate)

Nucleotide Oligonucleotide Nucleic Acid

Amino Acid Peptid e Polypeptide

Protein

Table 5.1

An Overview of Protein Functions

Describing Macromolecular Structure

Amino group Carboxyl group

α carbon α-Amino Acids

H3N C C O OH

+

R

H

H3N C C O O

+

R

H

H2N C C O O

R

H

- H+ + H+

- H+ + H+

+1 Charge 0 Charge -1 Charge

At low pH pH ~7 at high pH

Stereochemistry -- Tetrahedral α-Carbon

L-Alanine D-Alanine

α-Carbon C

C

C

O O

N

C

C

C

O O

N

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

20 Different Amino Acids Are Found in Proteins

Nonpolar side chains; hydrophobic Side chain

Glycine (Gly or G)

Alanine (Ala or A)

Valine (Val or V)

Leucine (Leu or L)

Isoleucine (Ile or I)

Methionine (Met or M)

Phenylalanine (Phe or F)

Tryptophan (Trp or W)

Proline (Pro or P)

Fig. 5.16a: Non-polar, hydrophobic aliphatic and aromatic amino acids often cluster together and are found in the interior of proteins

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)

Side chain-O-H Side chain-O-P-O- O

O-

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)

Side chain-O-H Side chain-O-P-O- O

O-

O-PO3 O-PO3

Aspartic acid (Asp or D)

Glutamic acid (Glu or E)

Lysine (Lys or K)

Arginine (Arg or R)

Histidine (His or H)

Note: similar size and shape

but different chemical properties

Glutamine (Gln) Q Glutamic Acid (Glu) E

Asparagine (Asn) N Aspartic Acid (Asp) D

Aromatic side chains (F,W,Y)

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)

Tyrosine (Tyr) Y Phenylalanine (Phe) F Tryptophan (Trp) W

Special cases:

Glycine is the smallest amino acid and its small side chain can fit into small spaces in protein

Glycine (Gly) G

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

The sulfhydryl group (-S-H) of two cysteines can react to form a covalent

disulfide bridge (-S-S-) Cysteine (Cys) C

Alanine (Ala) Aliphatic hydrophobic

Phenylalanine (Phe) Aromatic hydrophobic

Serine (Ser) Polar uncharged

Aspartic Acid (Asp) Acidic

Lysine (Lys) Basic

Amino Acids Whose Structures You Need to Know

Fig. 5.17: Peptide Bonds Link Amino Acids

Peptide bond

New peptide bond forming

Side chains

Back- bone

Amino end (N-terminus)

Peptide bond

Carboxyl end (C-terminus)

Peptide Bond: How proteins (polypeptides) are made from amino acids?

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.

H3N C C O OH

+

R1

H

N C C O O-

R2

H

H

H

H2O

N C C O O-

R2

H

H3N C C O +

R1

H

Amide bond

C C N C O

H

H

Lone electron pair on N forms second bond

C C N C O -

+ C C N C

O

H H or

The Peptide Bond group is Polar and Planar

(the atoms lie on a plane)

Cα C N Cα O

H

δ-

δ+

Main Chain

Side Chain

Amino Terminus Carboxy Terminus

Peptide Bond: Structural characteristics

Cα Cα C

C Cα N

N

H

H O

O

Planar Peptide Bond groups joined at Cα’s

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

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°

Aspartame a.k.a. NutraSweet - Is a Dipeptide

.5 Å

Secondary Structure: Local folding of the polypeptide backbone

1.5 Å

Hydrogen Bond

3.6 residues/turn 5.4 Å Hydrogen

Bond

Fig. 5.18: Tertiary Structure Describes overall fold of polypeptide backbone

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

β-sheet

α-helices

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

Tertiary Structure

β pleated sheet

Examples of amino acid subunits

+H3N Amino end

α helix

Quaternary Structure

Level of Structure

Type of Bond

Hydrophobic Bond most important + others

Between peptide bond groups

Primary Structure

Secondary and Tertiary Structures

Quaternary Structure Function Red Blood

Cell Shape

β subunit

β subunit β

β

α

α

Exposed hydrophobic region

Molecules do not associate with one another; each carries oxygen.

Molecules crystallize into a fiber; capacity to carry oxygen is reduced.

Sickle-cell hemoglobin

Normal hemoglobin

10 µm

10 µm

Sick

le-c

ell h

emog

lobi

n N

orm

al h

emog

lobi

n 1 2 3 4 5 6 7

1 2 3 4 5 6 7

β

β α

α

Fig. 5.22: Changing A Proteins’s Amino Acid Sequence Can Change Its Shape

Normal protein Denatured protein

Denaturation

Renaturation

Fig. 5.23: Amino Acid (primary structure) Sequence Determines Shape

(Biologically active) (Biologically inactive)

increase temperature, change pH, add chemical agents that disrupt hydrogen bonds,

ionic bonds and disulfide bridges

(Unfolding)

Folding (spontaneous)

Anfinsen experiment (1965)

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

Hemoglobin Photosynthetic Reaction Center (membrane protein)

Antibodies

http://www.sci.sdsu.edu/TFrey/ProtStructClass/

Photosynthetic Reaction Center (membrane protein)

Membrane Proteins: Some are a single polypeptide others have Quaternary Structure

Bacteriorhodopsin Bacterial Porin

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