1. Proteins Chapter 22

2. Proteins (Greek = “of first importance”) Functions: –Structure - skin, bones, hair, fingernails –Catalysis - biological catalysts are enzymes –Movement - muscle: actin and myosin –Transport - hemoglobin, transport thru membranes

3. Proteins Functions: –Hormones - insulin, oxytocin, HGH, etc. –Protection - antigen-antibody reactions, fibrinogen in clotting –Storage - casein in milk, ovalbumin in eggs, ferritin in liver-stores iron –Regulation - control in expression of genes

4. Proteins Protein types: –9000 different proteins in a cell –Individual human being >100,000 different –Fibrous Protein Insoluble in H 2 O Used mainly for structural purposes –Globular Protein Partly soluble in H 2 O Usually not used for structural purposes

5. Proteins are Natural Polymers Proteins are constructed in the body from many repeating units call amino acids Just like other polymers the amino acids (monomers) are joined together to make long chains (polymers) – but we call them proteins instead All of the polymer information applies to proteins – cross linking, rings, polarity etc.

6. Amino Acids The Building Blocks of proteins –Contains an amino group and an acid group –Nature synthesizes about 20 common AA –All but one (proline) fit this formula: –AA Proline:

7. Amino Acids Amino Acids (AA) –The twenty common are Called alpha amino acids –One and three letter codes given to 20 common AA –All but glycine (where R=H) exist as a pair of enantiomers nature usually produces the L amino acid LOOK IN THE BOOK

8. Amino Acids Amino Acids (AA) –Sometimes classified as AA with: nonpolar R groups polar but neutral R groups acidic R groups basic R groups

9. Zwitterions An acid -COOH and an amine -NH 2 group cannot coexist The H + migrates to the -NH 2 group COO - and NH 3 + are actually present, called a “Zwitterion”

10. Zwitterions Zwitterion = compound where both a positive charge and a negative charge exist on the same molecule AA are ionic compounds They are internal salts In solution their form changes depending on the pH AA’s

11. Zwitterions pH = 1-5 excess H + excess OH - pH = 10-14 more basic more acidic AA’s

12. Zwitterions pH = 1-5 excess H + excess OH - pH = 10-14 more basic more acidic at pI (isoelectric point) charge = 0 AA’s

13. pI The pI is the “isoelectric point” The pI is the pH where NO charge is on the AA: at pI charge = 0 (Not necessarily at a neutral pH)

14. Cysteine The AA Cysteine exists as a dimer: a disulfide linkage AA’s

15. Peptides AA are also called peptides They can be combined to form... AA’s

16. Peptides AA are also called peptides They can be combined to form a dipeptide. a peptide bond

17. Peptides Known as a “dipeptide” a peptide bond amine end acid end glycylalanine (Gly-Ala), a dipeptide

18. Peptides Glycylalanine is not the same as Alanylglycine glycylalanine alanylglycine

19. Peptides Synthesis of Alanylglycine alanylglycine

20. Peptides Addition of peptides (head to tail) –Formation of: dipeptides tripeptides tetrapeptides pentapeptides polypeptides PROTEINS AA’s

21. Student Practice Show the product for the following combination of amino acids Glu – Pro – His Pro – Asn – Leu Val – Ala – Trp

22. http://www.youtube.com/watch?v=va0DNJId _CM

23. Proteins Proteins usually contain about 30+ AA AA known as residues –One letter abbreviations G, A, V, L –Three letter abbreviations Gly, Ala, Val, Leu N terminal AA (amine end) on LEFT C terminal AA (carboxyl end) on RIGHT glycylalanineGly-AlaG-A AA’s

24. Polypeptides peptide bonds side chains amino acid residues AA’s

25. Solubility Polypeptides or Proteins –If there is a charge on a polypeptide, it is more soluble in aqueous solution –If there is NO CHARGE (neutral at pI), it is LEAST SOLUBLE in solution charged

26. Protein Structure Primary Structure 1 o –Linear sequence of AA Secondary Structure 2 o –Repeating patterns (  helix,  pleated sheet) Tertiary Structure 3 o –Overall conformation of protein Quaternary Structure4 o –Multichained protein structure

27. Protein Structure Primary Structure 1 o –Linear sequence of AA AA 1AA 2AA 3AA 4AA 5AA 6 With any 6 AA residues, the number of possible combinations is 6 x 6 x 6 x 6 x 6 x 6 = 46656 AA’s

28. Protein Structure Primary Structure AA 1AA 2AA 3AA 4AA 5AA 6 With any 6 of the 20 common AA residues, the number of possible combinations is 20 x 20 x 20 x 20 x 20 x 20 = 64,000,000 (and this is not nearly large enough to be a protein!) AA’s

29. Protein Structure Primary Structure –A typical protein could have 60 AA residues. This would have 20 60 possible primary sequences. 20 60 = 10 78 This results in more possibilities for this small protein than there are atoms in the universe!

30. Protein Structure Primary Structure –Sometimes small changes in the 1 o structure do not alter the biological function, sometimes they do. AA’s

31. Changes and Effect of AA change Cattle and hog insulin is used for humans but is different Sickle cell anemia – only one change in an amino acid – changes the hemoglobin From yahoo images

32. youtube http://www.youtube.com/watch?v=bCOJkp L7MVwhttp://www.youtube.com/watch?v=bCOJkp L7MVw

33. Protein Structure Secondary Structure –Repeating patterns within a region –Common patterns  helix  pleated sheet –Originally proposed by Linus Pauling Robert Corey AA’s

34. Protein Structure Secondary Structure  helix –Single protein chain –Shape maintained by intramolecular H bonding between -C=O and H-N- –Helical shape  helix is clockwise AA’s

35. YOUTUBE http://www.youtube.com/watch?v=yh9Cr5n2 1EE http://www.youtube.com/watch?v=XKI0le9e2 D8

36. Protein Structure Secondary Structure  pleated sheet –Several protein chains –Shape maintained by intramolecular H bonding and other attractive forces between chains –Chains run anti-parallel and make U turns at ends AA’s

37. Protein Structure Secondary Structure Random Coils –Few proteins have exclusively  helix or  pleated sheet –Many have non-repeating sections called: Random Coils AA’s

38. Collagen Protein Structure Secondary Structure Triple Helix of Collagen –Structural protein of connective tissues bone, cartilage, tendon aorta, skin –About 30% of human body’s protein –Triple helix units = tropocollagen AA’s

39. Youtube http://www.youtube.com/watch?v=YmuFI1jtc 8M&feature=PlayList&p=C8887E4E7D367 515&index=0&playnext=1 http://www.youtube.com/watch?v=gXeYf9dL T3s

40. Tertiary Structure –The Three dimensional arrangement of every atom in the molecule –Includes not just the peptide backbone but the side chains as well –These interactions are responsible for the overall folding of the protein –This folding defies its function and it’s reactivity AA’s

41. Tertiary Structure The Tertiary structure is formed by the following interactions: Covalent Bonds Hydrogen Bonding Salt Bridges Hydrophobic Interactions Metal Ion Coordination AA’s

42. Tertiary Structure –Covalent Bonding The most common covalent bond in forming the tertiary structure is the disufide bond It is formed from the disulfide Interaction of cysteine

43. Tertiary Structure –Hydrogen Bonding Anytime you have a hydrogen connected to a F O of N – you can get hydrogen bonding These interactions can occure on the side chain, backbone or both

44. Tertiary Structure –Salt Bridge Salt bridges are due to charged portions of the protein. Opposite charges will attract and Form ionic bonds Some examples are the NH 3 + and COO - areas of the protein

45. Tertiary Structure –hydrophobic interactions Because the nonopolar groups will turn away from the water and the polar groups toward it, hydrophobic interactions take place. These interactions are strong enough to help define the overall structure of a protein

46. Tertiary Structure –Metal Ion Coordination Two side chains with the same charge would normally repel each other However, if a metal is placed between them, they will coordinate to the meal and be connected together. These metal coordinations are Important in tertiary structure formation

47. Tertiary Structure

48. Quaternary Structure –Highest level of organization –Determines how subunit fit together –Example Hemoglobin (4 sub chains) 2 chains 141 AA 2 chains 146 AA - Example - Collagen

50. Denaturation –Any physical or chemical agent that destroys the conformation of a protein is said to “denature” it –Examples: Heat (boil an egg) to gelatin Addition of 6M Urea (breaks H bonds) Detergents (surface-active agents) Reducing agents (break -S-S- bonds)

51. Denaturation –Examples: Acids/Bases/Salts (affect salt bridges) Heavy metal ions (Hg 2+, Pb 2+ ) –Some denaturation is reversible Urea (6M) then add to H 2 O –Some is irreversible Hard boiling an egg

52. Denaturation