1. Proteins
Dr. Ron Rusay
Spring 2004
© Copyright 2004 R.J. Rusay

2. Biochemistry The chemistry of living organisms is called biochemistry.
Some important biochemical molecules are polymers.
Biopolymers fall into three classes:
Proteins
Nucleic acids (DNA & RNA)
Polysaccharides (complex carbohydrates)

3. Proteins
Amino Acids
Proteins are large molecules present in all cells.
They are made up of -amino acids.
There are about 20 amino acids (22) found in most proteins.
Each amino acid is assigned either a one or a three-letter abbreviation.

4. Proteins
Natural polymers made up of -amino acids [molecular weights range from  6000 to >1,000,000 g/mol (daltons)].
Fibrous Proteins: provide structural integrity and strength to muscle, hair and cartilage.
The rotating image above is collagen, a fibrous protein found in skin, bone, muscle and connective tissue. It accounts for about 30% of all protein in humans. Collagen is a molecule made up of 3,000 amino acids which are evenly distributed in three intertwined, cross-linked chains.

5. Proteins (continued) Globular Proteins: act as catalysts.
are roughly spherical in shape.
General Functions:
provide molecular and electron transport.
counter invasion by “foreign” chemicals.
regulate the body’s metabolic systems.

6. -Amino Acids
NH2 always attached to the -carbon (the carbon attached to COOH)
C = -carbon
Linking:
(Amide bond)

7. Proteins
Amino Acids

8. Proteins
Amino Acids
The enantiomer that rotates the plane of polarized light to the left is called L- (laevus = “left”) and the other enantiomer is called D- (dexter = right).
Enantiomers have identical physical and chemical properties. They only differ in their interaction with other enantiomers.
Most amino acids in proteins exist in the L-form.

9. Proteins Amino Acids Our bodies can synthesize about 10 amino acids.
Essential amino acids are the other 10 amino acids, which have to be ingested.
The -carbon in all amino acids except glycine is chiral (has 4 different groups attached to it).
Chiral molecules exist as two non-superimposable mirror images.
The two mirror images are called enantiomers.
Chiral molecules can rotate the plane of polarized light.

10. Proteins
Amino Acids

11. Proteins
Amino Acids

13. Protein Bonds & -Amino Acids
Amino acids combine to form a peptide Bond + H2O

A peptide linkage
There are 20 (22) different amino acids that are commonly found in proteins.

17. Levels of Protein Structure
Primary: The sequence of amino acids in the protein chain. Acetylcholinesterase Sickle Cell, Anemia
Secondary: The arrangement of the protein chain in the long molecule. Helices & Sheets.
Tertiary: The overall shape of the protein strand
Quaternary: The aggregate shape including all of the strands. Eg. Hemoglobin: 2  and 2 

18. Proteins: Size, Shape & Self Assembly
Catalysis - can increase reaction rates by factors of 10 6 to 10 12
Regulation - Hormones
Transport - primarily across membranes. Lipoproteins carry lipids in bloodstream.
Structure - For example, collagen
Movement - Changes in configuration of proteins in muscle are responsible for muscle contraction.
Defense - skin, blood-clotting, antibodies, ...

19. Proteins
Protein Structure

22. Protein Shape: Forces, Bonds, Self Assembly,
Folding
15-16
Title:
Tertiary Interactions
Caption:
The four distinct interactions that stabilize tertiary protein structures.
Notes:
Note that the disulfide bridge is a covalent bond.
Ion-dipole
(Dissolving)
40-600kJ/mol
10-40kJ/mol
kJ/mol
kJ/mol
700-4,000kJ/mol

23. Tertiary Structure: The overall shape of the protein strand (determined by hydrogen-bonding, dipole-dipole interactions, ionic bonds, covalent bonds and London forces).

25. Eg. Hemoglobin: 2  and 2  chains
The aggregate shape including all of the strands.
Eg. Hemoglobin: 2  and 2  chains

26. Human’s total ~ 100 x 10 6 immunoproteins
Antibodies
Prolific Immunoproteins
Immunoglobin
Human’s total ~ 100 x 10 6 immunoproteins
Combinatorial syntheses from libraries of 250, 10, and 6 possible contributors
Human Genome ~30,000 proteins

27. Enzymes
Highly specialized proteins which catalyze specific biologic reactions.

28. Enzymes (continued)
A “lock-and-key” model explains the enzyme’s mechanism.
A “substrate” and enzyme interact via
H-bonding
ionic bonding and/or
metal ion-ligand bonding
The substrate occupies a highly specific “active site” of the enzyme.

29. Acetylcholinesterase Docking
Richard Short (Cornell University)

30. Models, Theories & Interactions
Molecular Shape & the Sense of Smell
Structure-Odor Relationships
Karen J. Rossiter, Chem. Rev., 1996, 96,

31. Three different smell receptors.

32. Four different molecules fitting the same smell receptor.
Modeling and Smell
Four different molecules fitting the same smell receptor.

33. Shapes & Interactions: Mirror Images & Smell
S-(+)-d-
R-(-)-l-
S-(+)- caraway R-(-)- spearmint

34. Acetylcholine, Nerves & Neurotransmission
The Neuron: Shapes and Spaces
20-04
Title:
Acetylcholine
Caption:
The mechanism of action by the neurotransmitter acetylcholine.
Notes:
Acetylcholine is destroyed by esterase enzymes.

35. Acetylcholine: OP Pesticides and Nerve gases
20-05
Title:
Acetylcholinesterase
Caption:
Inhibition of acetylcholinesterase.
Notes:
Nerve agents form a covalent bond to the enzyme and cause irreversible inhibition.