1. Chemistry 2100
Lecture 10

2. Proteins Proteins serve many functions, including the following.
1. Structure: Collagen and keratin are the chief constituents of skin, bone, hair, and nails.
2. Catalysts: Virtually all reactions in living systems are catalyzed by proteins called enzymes.
3. Movement: Muscles are made up of proteins called myosin and actin.
4. Transport: Hemoglobin transports oxygen from the lungs to cells; other proteins transport molecules across cell membranes.
5. Hormones: Many hormones are proteins, among them insulin, oxytocin, and human growth hormone.

3. Proteins Proteins are divided into two types:
6. Protection: Blood clotting involves the protein fibrinogen; the body used proteins called antibodies to fight disease.
7. Storage: Casein in milk and ovalbumin in eggs store nutrients for newborn infants and birds. Ferritin, a protein in the liver, stores iron.
8. Regulation: Certain proteins not only control the expression of genes, but also control when gene expression takes place.
Proteins are divided into two types:
Fibrous proteins
Globular proteins

4. • nonpolar
• polar / neutral
• acidic / basic

5. Chirality of -Amino Acids
With the exception of glycine, all protein-derived amino acids have at least one stereocenter (the -carbon) and are chiral.
The vast majority of -amino acids have the L-configuration at the -carbon.

6. • nonpolar
• polar / neutral
• acidic / basic

7. Protein-Derived -Amino Acids
Nonpolar side chains (at pH 7.0)

8. Protein-Derived -Amino Acids
Polar side chains (at pH 7.0)

9. Protein-Derived -Amino Acids
Acidic and basic side chains (at pH 7.0)

10. essential amino acids
Leu, Ile, Lys, Met, Phe, Thr, Trp, Val, His ( Arg, Tyr, Cys )

12. Ionization vs. pH
The net charge on an amino acid depends on the pH of the solution in which it is dissolved.
If we dissolve an amino acid in water, it is present in the aqueous solution as its zwitterion.
If we add a strong acid such as HCl to bring the pH of the solution to 0.0, the strong acid donates a proton to the -COO- of the amino acid turning the zwitterion into a positive ion.

13. Ionization vs. pH
If we add a strong base such as NaOH to the solution and bring its pH to 14, a proton is transferred from the NH3+ group to the base turning the zwitterion into a negative ion.
To summarize:

14. Problem: Calculate the net charge of lysine at pH = 3, 7, 11
Problem: Calculate the net charge of lysine at pH = 3, 7, 11. Estimate pI for lysine.

15. pH = 7

16. (–)
pH = 7

17. (–)
(+)
pH = 7

18. (–)
(+)
(+)
pH = 7

19. (–)
(+)
(+)
pH = 7

20. (–)
(+)
(+)
pH = 3
pH = 7

21. (–)
(+)
(+)
(+)
(+)
pH = 3
pH = 7

22. (–)
(+)
(+)
(+)
(+)
pH = 3
pH = 7
pH = 11

23. (–)
(–)
(+)
(+)
(+)
(+)
pH = 3
pH = 7
pH = 11

24. Isoelectric Point (pI)
The pH at which the majority of molecules of a compound in solution have no net charge.

25. Problem: Predict the electrophoresis behavior at pH 6
Problem: Predict the electrophoresis behavior at pH 6.0 of a mixture of
alanine (pI 6.0), aspartic acid (pI 2.8) and lysine (pI 9.7)

26. Problem: Predict the electrophoresis behavior at pH 6
Problem: Predict the electrophoresis behavior at pH 6.0 of a mixture of
alanine (pI 6.0), aspartic acid (pI 2.8) and lysine (pI 9.7)

27. Problem: Predict the electrophoresis behavior at pH 6
Problem: Predict the electrophoresis behavior at pH 6.0 of a mixture of
alanine (pI 6.0), aspartic acid (pI 2.8) and lysine (pI 9.7)

28. alanine (pI 6.0), aspartic acid (pI 2.8) and lysine (pI 9.7)
Problem: Predict the electrophoresis behavior at pH 6.0 of a mixture of
alanine (pI 6.0), aspartic acid (pI 2.8) and lysine (pI 9.7)
Lys Ala Asp

29. Peptide Bonds

30. Peptide Bonds

31. Peptide Bonds

32. Peptide Bonds

33. Peptide Bonds

39. (C-terminus) (N-terminus)
(+)
(–)
(+)
(–)
(+)
lysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]

40. (C-terminus) (N-terminus)
(+)
(–)
(+)
(–)
(+)
lysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]

41. (C-terminus) (N-terminus)
(+)
(–)
(+)
(–)
(+)
lysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]

42. (C-terminus) (N-terminus)
(+)
(–)
(+)
(–)
(+)
lysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]

43. (C-terminus) (N-terminus)
(+)
(–)
(+)
(–)
(+)
lysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]

44. (C-terminus) (N-terminus) pH = 7
(–)
(–)
lysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]
pH = 7

45. (C-terminus) (N-terminus) pH = 7
(+)
(–)
(+)
(–)
(+)
lysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]
pH = 7

46. (C-terminus) (N-terminus) pH = 3
(+)
(–)
(+)
(–)
(+)
lysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]
pH = 3

47. (C-terminus) (N-terminus) pH = 3
(+)
(–)
(+)
(–)
(+)
lysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]
pH = 3

48. (C-terminus) (N-terminus) pH = 11
(–)
(–)
lysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]
pH = 11

49. (C-terminus) (N-terminus) pH = 11
(–)
(–)
lysylserylmethionylaspartylarginine [Lys–Ser–Met–Asp–Arg]
pH = 11

50. (5!) = combinations
(20!) =  eicosapeptides
(205) =  possible pentapeptides

51. (5!) = combinations
(20!) =  eicosapeptides
(205) =  possible pentapeptides

52. (5!) = combinations
(20!) =  eicosapeptides
(205) =  possible pentapeptides

53. (5!) = combinations
(20!) =  eicosapeptides
(205) =  possible pentapeptides

54. (5!) = combinations
(20!) =  eicosapeptides
(205) =  possible pentapeptides

55. (5!) = combinations
(20!) =  eicosapeptides
(205) =  possible pentapeptides

56. oxytocin
vasopressin

57. Methionine enkephalin
Enkephalins
Morphine
Tyr–Gly–Gly–Phe–Leu
Leucine enkephalin
Tyr–Gly–Gly–Phe–Met
Methionine enkephalin

58. Insulin S S 5 10 15 20
Gly–Ile–Val–Glu–Gln–Cys–Cys–Thr–Ser–Ile–Cys–Ser–Leu–Tyr–Gln–Leu–Glu–Asn–Tyr–Cys–Asn S S S S 5 10 15 20 25 30
Phe–Val–Asn–Gln–His–Leu–Cys–Gly–Ser–His–Leu–Val–Glu–Ala–Leu–Tyr–Leu–Val–Cys–Gly–Glu–Arg–Gly–Phe–Phe–Tyr–Thr–Pro–Lys–Thr

59. Structure of Proteins

64. Secondary Structure: The -Helix

65. -Pleated Sheet

66. Random Coil

67. -pleated sheet
-helix
-helix
-pleated sheet

68. Protein Tertiary Structure

69. -pleated sheet
-helix
-helix
-pleated sheet

70. -pleated sheet
-helix
salt bridge
-helix
-pleated sheet

71. -pleated sheet
-helix
salt bridge
-helix
hydrogen
bond
-pleated sheet

72. -pleated sheet
-helix
hydrogen
bond
salt bridge
-helix
hydrogen
bond
-pleated sheet

73. hydrophilic
interaction
to water
-pleated sheet
-helix
hydrogen
bond
salt bridge
-helix
hydrogen
bond
-pleated sheet

74. hydrophilic
interaction
to water
-pleated sheet
-helix
hydrogen
bond
hydrophobic
interaction
salt bridge
-helix
hydrogen
bond
-pleated sheet

75. hydrophilic
interaction
to water
-pleated sheet
-helix
hydrogen
bond
hydrophobic
interaction
salt bridge
-helix
hydrogen
bond
-pleated sheet

76. hydrophilic
interaction
to water
-pleated sheet
-helix
hydrogen
bond
hydrophobic
interaction
salt bridge
disulfide
bond
-helix
hydrogen
bond
-pleated sheet

77. Protein Quaternary Structure

78. Hemoglobin
C3032H4816N735O780S8Fe4 (MW 64,450)

79. Sickle-Cell Anemia

80. Sequence Varies: Ask 23andMe

81. Proteins

82. Denaturation

83. Denaturation… also known as “Cooking”

84. Misfolding Diseases

85. Mutation Impairs Proper Folding
Sickle Cell
Anemia
Cystic Fibrosis

86. Contagious Misfolding: Prions