1. Proteins & Other Macromolecules
Carbon and Functional Groups Polymerization as a Theme Lipids Carbohydrates Nucleic Acids Proteins polymers of amino acids the peptide bond four levels of protein structure folding patterns protein domains prosthetic groups

2. On the Web Site:
Week 6 Reading
Homework due Saturday!

3. office hours today: 12-1 (lunch) 1-4 (office)
Resources needed for the Homework are in the Week 5 Folder (be sure to check the FlyLab hints!)
office hours today: 12-1 (lunch) 1-4 (office)

4. There’s a special “Handout” for today on the Week 5 page:
The Linus Pauling alpha-helix construction kit!

5. 1) The chemistry of life is the chemistry of carbon
1) The chemistry of life is the chemistry of carbon. Carbon’s almost unlimited ability to bond to itself makes it possible to form macromolecules of great length & complexity (MWs may exceed 1,000,000.
single
covalent
bond
branching from backbone
carbon backbone
carbon
atom or
carbon rings

6. Amino Carbonyl Carboxyl Hydroxyl Phosphate Sulfhydryl
2) Carbon chemistry can be understood in terms of functional groups:
Amino Carbonyl Carboxyl Hydroxyl Phosphate Sulfhydryl
Why name groups?
They enable us to predict (in a general way) the behavior of molecules containing them.
See Freeman p. 40

7. carboxyl amino C O H C O H + - N H + H N H+ ion donor = organic acid.
H+ ion acceptor = organic base.

8. H2N
Amino
group C
Side chain R H O OH
Carboxyl
Non-ionized form

9. H O H3N+ C C O- R Ionized form (in water) Amino group Carboxyl group
Side chain

10. The presence of similar chemical groups in two molecules tells us that they will have some properties in common. (Example: amino and carboxyl groups in both of these molecules)

11. Living things are based on “macromolecules”
• No precise definition (MW > 1,000 d)
• Usually assembled from simpler subunits by the process of polymerization:
homopolymer
monomer
heteropolymer
dimer
trimer
tetramer
polymer

12. Lipids Carbohydrates Nucleic Acids Proteins
Four major classes of biological macromolecules:
Lipids
Carbohydrates
Nucleic Acids
Proteins

13. Lipids Carbohydrates Nucleic Acids Proteins Hydrocarbon chain
Fatty Acid
Triglyceride (a lipid)
Fats (Lipids) are macromolecules that are waxy or oily and soluble in organic solvents (such as ethanol, acetone, benzene)

14. Many lipids have water-loving & water-hating portions
Phospholipid
Formula
Schematic
Space-filling
Icon
NH3+ HC
COOH
Polar head
(hydrophilic)
CH2 O– O P O–
Serine H O
H2C C
CH2
Phosphate O O
Glycerol C O C O
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
Fatty acid
Fatty acid
Nonpolar tail
(hydrophobic)
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH3
CH3

15. Making them particularly good at forming membranes

16. Extracellular matrix (carbohydrate & protein)
Glycoproteins
Extracellular matrix (carbohydrate & protein)
Lipid Bilayer
Membrane proteins
Cytoskeletal proteins

17. saturated unsaturated Poly-unsaturated stearic acid oleic acid
linolenic acid

18. Lipids Carbohydrates Nucleic Acids Proteins Glucose: C6H12O6
Carbohydrates have the general formula (CH2O)n where n>3.
Glucose: C6H12O6

19. When the linear form closes to form a ring, the position of the —OH group on carbon #1 determines if it will close in the α or β form

20. Lipids Carbohydrates Nucleic Acids Proteins
Glucose is a monosaccharide (or, “simple sugar”).
Lipids
Carbohydrates
Nucleic Acids
Proteins
…which can be joined to other sugars to form disaccharides - or polysaccharides

21. Lipids
Carbohydrates
Nucleic Acids
Proteins
Starch
Glucose

22. 6 C H O H C H O H C H O H C H O H C H O H 2 2 2 2 2 5 O H O H O H O H O H H O H H H H H O H H 1 O 4 O H H 1 O O H H O O H H O O H H H O H H H H H 3 2 H O H H O H H O H H O H H O H c e l l u l o s e 6 C H O H C H O H C H O H C H O H C H O H 2 2 2 2 2 H O H H 5 O H H O O H H O H H H H H H H H O H H 1 4 O H H 1 O H H O H H O H H O O O O O H O H 3 2 H O H H O H H O H H O H H O H a m y l o s e
Starch and cellulose are both polymers of glucose. Monomers of starch are linked by α-1,4 glycosidic bonds. Cellulose by β-1,4 glycosidic bonds.

23. Nucleic Acids are polymers of nucleotides
Purines
Pyrimidines

24. RNA (ribonucleic acid) and DNA (deoxyribonucleic acid) are formed by joining nucleotides into long chains

25. Nucleotides are also used in a variety of other cellular roles, including cell signaling and the regulation of metabolism:

26. R NH2 C COOH H Proteins are polymers of amino acids
All Amino Acids possess:
an α-carbon atom, bonded to:
• COOH (carboxyl) • NH2 (amino) • H (hydrogen) • another chemical group (—R)

27. The 20 common amino acid R-groups include chemical groups of every size and type.
Amino acids can be thought of as a “construction kit” from which molecules with almost any chemical property can be assembled.

28. Amino Acids are joined by covalent bonds between amino and carboxyl groups:
H2O

29. A “peptide bond” is a covalent bond formed between the carbon of a carboxyl group and the nitrogen of an amino group.
A polypeptide chain has an amino terminus and a carboxy terminus:

30. is a different molecule from
The two ends of a polypeptide chain are chemically different. As a result,
N-ala-gly-cys-C
is a different molecule from
N-cys-gly-ala-C

31. N H C O
A peptide bond has partial double bond character. This prevents free rotation around it. In the C-C-N backbone of a polypeptide chain, there is free rotation around only one atom: the alpha carbon of each amino acid N H C O + -

32. Freeman (4/e) Fig. 3.8, p. 44

33. X-ray crystallography can be used to determine the structure of proteins at the atomic level.

34. But diffraction patterns are complex, and difficult to interpret.
Pauling is one of just two people to win Nobel Prizes in two fields - and the only person ever to win two unshared Nobel Prizes.
Enter Linus Pauling:
Pauling realized that certain patterns of diffraction spots appeared over and over again in many different proteins.
He suspected that there might be regions of these proteins that folded into a particular, repeating pattern - and set about trying to figure it out.

35. One day, in 1948, he drew a diagram of a polypeptide chain, taking care to get the bond angles exactly right:
Suddenly, he realized that this chain could be folded in a way that actually predicted the diffraction spots.

37. Key features of the α−Helix: Stabilized by H-bonds between amino and carboxyl groups in polypeptide chain. R-groups stick out to side of helix (exposed to exterior). Only one amino acid cannot fold into the helix pattern (Proline).

38. It is stabilized by Hydrogen Bonds between amino & carboxyl groups.
The α-Helix is a folding pattern repeated over and over again in many proteins.
It is stabilized by Hydrogen Bonds between amino & carboxyl groups.

39. ... which contains many α- helical regions.
John Kendrew shared the Nobel Prize in for using X-ray diffraction to solve the structure of myoglobin...
... which contains many α- helical regions.
But many parts of the protein are not α-helical!

40. It is also held together by Hydrogen Bonds.
Antiparallel beta-sheet
Meaning: the α-helix is just one way in which a polypeptide chain can fold.
Another is the β-sheet, worked out by Pauling and Robert Corey in 1951.
It is also held together by Hydrogen Bonds.
And there are many other patterns as well, although these are less common than the α-helix and β-sheet

41. Key features of the β−sheet: Stabilized by H-bonds between amino and carboxyl groups in opposite polypeptide chains. R- groups stick out above and below sheet. Adjacent sheets may be anti-parallel (shown above) or parallel.

44. β-sheet structure

45. Myoglobin is a relatively simple protein - and yet its structure is very complex.
Or, we could describe the structure in a way that makes comparison easy, by emphasizing different structural levels
How should we describe the structure of a protein? One (unsatisfactory) way would be to treat each protein as unique.

46. Secondary Structure (local folding of chain)
Tertiary Structure (polypeptide folding in 3D)
Primary Structure (AA sequence)
Quaternary Structure (subunits)

47. An Example:
Lysozyme (3 representations)

48. Primary
Secondary
Tertiary
Quarternary

49. A single amino acid sequence may contain regions with different secondary structures
Tertiary structure is the pattern in which these regions fold together.

50. Tertiary structure is stabilized by a variety of bonds:
Hydrogen bonds, ionic bonds
oxidants
reductants
Disulfide bonds (covalent)
hydrophobic “bonds”

51. Two cysteines may form disulfide bonds that stabilize tertiary or quaternary structure

52. A polypeptide contains the following amino acids:
12 glycines
7 isoleucines
8 cysteines
1 proline
7 alanines
6 threonines
3 glutamines
4 histidines
11 serines
Question: What is the maximum number of disufide bonds that can be formed within this polypeptide?

53. Tidbit #1: Some proteins can be artificially unfolded and then refolded by manipulation of their disulfide bonds:

54. Src protein kinase (a signaling protein)
Tidbit #2: A “protein domain” is any region of a protein that can independently fold into a compact, stable structure.
Src protein kinase (a signaling protein)

55. Quaternary structure is arrangement of individual polypeptides to form a multi-subunit protein.

56. heme
hemoglobin
retinal (in rhodopsin)
A Prosthetic group is a non-amino- acid portion of a protein. It may be as complex as heme, or as simple as a single zinc atom (carboxypeptidase)

57. A “polypeptide” is a polymer made up of amino acids joined by peptide bonds.
A “protein” is a functional molecular unit composed of one or more polypeptides and their associated prosthetic groups.
Question: Describe the quaternary structure of this protein in as much detail as possible.