Chapter 14

Proteins

Chemistry 20

Function of proteins

Fibrinogen helps blood clotting

Proteins

100,000 different proteins in human body.

Fibrous proteins:

Insoluble in water – used for structural purposes.

Globular proteins:

More or less soluble in water – used for nonstructural purposes.

• Are the building blocks of proteins.• Contain carboxylic acid and amino groups.• Are ionized in solution (soluble in water).

• They are ionic compounds (solids-high melting points).

• Contain a different side group (R) for each.

R side chain R

│ │

H2N— C —COOH H3N— C —COO−

│ │

H H ionized form

Amino acids

+Zwitterion

Amino acids

H │

H3N—C —COO−

│ H glycine

CH3 │

H3N—C —COO−

│ H alanine

+

+

Only difference: containing a different side group (R) for each.

Amino acids are classified as:

• Nonpolar amino acids (hydrophobic) with hydrocarbon (alkyl or aromatic) sides chains.

• Polar amino acids (hydrophilic) with polar or ionic side chains.

• Acidic amino acids (hydrophilic) with acidic side chains (-COOH).

• Basic amino acids (hydrophilic) with –NH2 side chains.

Amino acids

There are only 20 different amino acids in the proteins in humans.

There are many amino acids.

Amino acids

Are called α amino acids.

Nonpolar amino acids

NH3+

COO-

NH3+

COO-

NH3+

COO-

NH3+

COO-

NH3+

COO-S

NH3+

COO-

NH H

COO-

NH3+

COO-

NH

COO-

NH3+

Alanine (Ala, A)

Glycine (Gly, G)

Isoleucine (Ile, I)

Leucine (Leu, L)

Methionine (Met, M)

Phenylalanine (Phe, F)

Proline (Pro, P)

Tryptophan (Trp, W)

Valine (Val, V)

NH3+

COO-

HS

NH3+

COO-

HO

Cysteine (Cys, C)

Tyrosine (Tyr, Y)

NH3+

COO-H2N

O

NH3+

COO-

H2N

O

NH3+

COO-

HO

NH3+

COO-OH

Asparagine (Asn, N)

Glutamine (Gln, Q)

Serine (Ser, S)

Threonine (Thr, T)

Polar amino acids

NH3+

COO--O

O

NH3+

COO--O

O NH3+

COO-

NH

H2N

NH2+

NH3+

COO-

N

NH

NH3+

COO-H3N

Glutamic acid (Glu, E)

Aspartic acid (Asp, D)

Histidine (His, H)

Lysine (Lys, K)

Arginine (Arg, R)

+

Acidic and basic amino acids

Fischer projections

All of the α-amino acids are chiral (except glycine)

Four different groups are attached to central carbon (α-carbon).

H NH3+

COO-

CH3

+H3N H

COO-

CH3

D-Alanine L-Alanine

(Fischer projections)

H NH3+

COO-

CH3

+H3N H

COO-

CH3

D-Alanine L-Alanine

(Fischer projections)

CH2SH CH2SH

D-cysteine L-cysteine

L isomers is found in the body proteins.

Ionization and pH

pH: 5 to 6 Isoelectric point (pI)

Positive charges = Negative chargesNo net charge - Zwitterion

pH: about 2 or 3

-COO- acts as a base and accepts an H+

+

RH3N-CH-C-O

-O

+ H3O+ +

RH3N-CH-C-OH

O+H2O

pH: 7.6 to 10.8 -NH3+ acts as an acid and loses an H+

+

RH3N-CH-C-O

-O

+ OH-

RH2N-CH-C-O

-O

+H2O

+

RH3N-CH-C-O

-O

+ OH-

RH2N-CH-C-O

-O

+H2O

-

Ionization and pH

The net charge on an amino acid depends on the pH of the solution in which it is dissolved.

pH 2.0 pH 5.0 - 6.0 pH 10.0Net charge +1 Net charge 0 Net charge -1

+

RH3N-CH-C-O

-O+

RH3N-CH-C-OH

O

RH2N-CH-C-O

-OOH-

H3O+

OH-

H3O+

6.015.41

5.655.976.026.025.745.486.485.685.87

5.895.97

pI

valinetryptophan

threonineserineprolinephenylalaninemethionineleucineisoleucineglycineglutamine

asparaginealanine

Nonpolar &polar side chains

10.76

2.77

5.073.22

7.599.74

5.66

pI

tyrosine

lysinehistidine

glutamic acidcysteine

aspartic acid

arginine

AcidicSide Chains

BasicSide Chains pI

Ionization and pH

Each amino acid has a fixed and constant pI.

A dipeptide forms:

• When an amide links two amino acids.

• Between the COO− of one amino acid and

the NH3 + of the next amino acid.

Peptide

O

O-H3N

CH3H3N O-

CH2OH

O

H3NN

CH3

O CH2OH

O

O-

H

H2O+

Alanine (Ala) Serine (Ser)

++

+

peptide bond

Alanylserine (Ala-Ser)

+

•Dipeptide: A molecule containing two amino acids joined by a peptide bond.

•Tripeptide: A molecule containing three amino acids joined by peptide bonds.

•Polypeptide: A macromolecule containing many amino acids joined by peptide bonds.

•Protein: A biological macromolecule containing at least 30 to 50 amino acids joined by peptide bonds.

Peptide

Naming of peptides

C-terminal amino acid: the amino acid at the end of the chain

having the free -COO- group.

N-terminal amino acid: the amino acid at the end of the chain

having the free -NH3+ group.

H3N

OH

NH O

HN

COO-

O-

OC6H5O

+

C-terminalamino acid

N-terminalamino acid

Ser-Phe-Asp

Naming of peptides

- Begin from the N terminal.

- Drop “-ine” and it is replaced by “-yl”.

- Give the full name of amino acid at the C terminal.

H3N-CH-C-NH-CH2-C-NH-CH-C-O

CH3 CH2OH

O O O

From alaninealanyl

From glycineglycyl

From serineserine

Alanylglycylserine(Ala-Gly-Ser)

+ -

Structure of proteins

1. Primary structure

2. Secondary structure

3. Tertiary structure

4. Quaternary structure

Primary Structure of proteins

- The order of amino acids held together by peptide bonds.

- Each protein in our body has a unique sequence of amino acids.

- The backbone of a protein.

Ala─Leu─Cys─Met

+

CH3

S

CH2

CH2

SH

CH2

CH3

CH3CH

CH O

O-CCH

H

N

O

CCH

H

N

O

CCH

H

N

O

C

CH3

CHH3N

+

Cysteine

The -SH (sulfhydryl) group of cysteine is easily oxidized

to an -S-S- (disulfide).

+

CH2

H3N-CH-COO-

SH

oxidation

reduction

+

CH2

H3N-CH-COO-

S

+H3N-CH-COO

-CH2

S

CysteineCystine

2

a disulfidebond

Primary Structure of proteins

Chain A

CO

O-

NH3+ NH3

+

CO

O-

Chain B

The primary structure of insulin:

- Is a hormone that regulates the glucose level in the blood.

- Was the first amino acid order determined.

- Contains of two polypeptide chains linked by disulfide bonds (formed by side chains (R)).

- Chain A has 21 amino acids and

chain B has 30 amino acids.

- Genetic engineers can produce it for treatment of diabetes.

Secondary Structure of proteins

Describes the way the amino acids next to or near to each otheralong the polypeptide are arranged in space.

1. Alpha helix (α helix)

2. Beta-pleated sheet (-pleated sheet)

3. Triple helix (found in Collagen)

Secondary Structure - α-helix

• A section of polypeptide chain coils into a rigid spiral.

• Held by H bonds between the H of N-H group and the O of C=O of the fourth amino acid down the chain (next turn).

• looks like a coiled “telephone cord.”

• All R- groups point outward from the helix.

H-bond

Secondary Structure - -pleated sheet

O H

• Consists of polypeptide chains arranged side by side.

• Has hydrogen bonds between the peptide chains.

• Has R groups above and below the sheet (vertical).

• Is typical of fibrous proteins such as silk.

Secondary Structure – Triple helix (Collagen)

- Collagen is the most abundant protein.

- Three polypeptide chains (three α-helix) woven together.

- Typical of collagen, connective tissue, skin, blood vessels, tendons, and cartilage.

- Consists of glycine (33%), proline (22%), alanine (12%), and smaller amount of hydroxyproline and hydroxylysine.

- We need vitamin C (special enzyme).

Tertiary Structure

The tertiary structure is determined by attractions and repulsions between the side chains (R) of the amino acids in a polypeptide chain.

Interactions between side chains of the amino acids fold a protein into a specific three-dimensional shape.

-S-S-

Tertiary Structure

(1) Disulfide (-S-S-)

(2) salt bridge (acid-base)(3) Hydrophilic (polar)(4) hydrophobic (nonpolar)(5) Hydrogen bond

Globular proteins

- Have compact, spherical shape.

- Almost soluble in water.

- Carry out the work of the cells: Synthesis, transport, and metabolism

Myoglobin

Stores oxygen in muscles.

153 amino acids in a single polypeptide chain (mostly α-helix).

Fibrous proteins

α-keratin: hair, wool, skin, and nails

- Have long, thin shape and insoluble in water.

- Involve in the structure of cells and tissues.

Three α-helix bond together by disulfide bond (-S-S-)

-keratin: feathers of birds

Large amount of -pleated sheet

Quaternary Structure

• Occurs when two or more protein units (polypeptide subunits) combine.

• Is stabilized by the same interactions found in tertiary structures (between side chains).

• Hemoglobin consists of four polypeptide chains as subunits.

• Is a globular protein and transports oxygen in blood (four molecules of O2).

chain

chain

α chain

α chain

Hemoglobin

Summary of protein Structure

Summary of protein Structure

Denaturation

Active protein

Denatured protein

- Is a process of destroying a protein by chemical and physical means.

- We can destroy secondary, tertiary, or quaternary structure but the primary structure is not affected.

- Denaturing agents: heat, acids and bases, organic compounds, heavy metal ions, and mechanical agitation.

- Some denaturations are reversible, while others permanently damage the protein.

Denaturation

•Heat: H bonds, Hydrophobic interactions

•Detergents: H bonds

•Acids and bases: Salt bridges, H bonds.

•Reducing agents: Disulfide bonds

•Heavy metal ions (transition metal ions Pb2+, Hg2+): Disulfide bonds

•Alcohols: H bonds, Hydrophilic interactions

•Agitation: H bonds, Hydrophobic interactions