1. 19-1 Principles and Applications of Inorganic, Organic, and Biological Chemistry Denniston, Topping, and Caret 4 th ed Chapter 19 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Power Point to Accompany

2. 19-2 Introduction Proteins: Provide nitrogen and sulfur for the diet Most abundant macromolecules in the cell Carry out most of the work of the cell

3. 19-3 19.1 Cellular Function of Proteins Are biological catalysts (enzymes) Are antibodies that fight antigens (bacteria and viruses) Transport molecules and ions Regulate cell function Provide structural support and mechanical strength Are necessary for all forms of movement Are sources of amino acids for growth

4. 19-4 Four Levels of Protein Structure Primary, 1 o the amino acid sequence Secondary, 2 o 3-D arrangement of backbone atoms in space Tertiary, 3 o 3-D arrangement of all the atoms in space Quaternary, 4 o 3-D arrangement of subunit chains

5. 19-5 19.2 The  -Amino Acids An alpha amino acid is a carboxylic acid with an amino group on the carbon alpha to the carboxylic acid. The alpha carbon also has an R group side chain except for glycine which has two Hs. Generic amino acid at physiological pH.  C

6. 19-6 If the R group is not H, the AA can exist in two enantiomeric forms (nonsuperimposable mirror image) forms.) Mirror plane  carbon Amino acids incorporated into proteins have the L- configuration.

7. 19-7 AA with nonpolar side chains-1

8. 19-8 AA with nonpolar side chains-2

9. 19-9 AA with polar side chains-1

10. 19-10 AA with polar side chains-2

11. 19-11 AA: acidic and basic

12. 19-12 19.3 The Peptide Bond A peptide is a polymer of about 2-100 amino acids linked by the peptide(amide) bond. As the amino group and the carboxyl group link, water is lost.

13. 19-13 Peptide Bond, Cont. There is restricted rotation about the peptide bond due to resonance. This restricted rotation has important consequences in terms of protein structures.

14. 19-14 Peptides: Structure and Names Structure left (N-term) to right (C-term) Structure is based on the repeating sequence N-C-C-N-C-C-N-C-C N is the  -amino group; white is the a-carbon; and yellow is the carbonyl carbon. Name peptides by prefixing (L to R) the amino acid name, the ending –ine changed to –yl, and terminating in the COOH end AA name. E. g. ala-gly is alanyl-glycine

15. 19-15 Names-cont. Glutathione: the reduced form Reduces oxidizing agents by dimerizing to form the disulfide bond with release of 2 H. N-terminalC-terminal

16. 19-16 Draw: alanyl-glycyl-valine (ala-gly-val) Draw the skeleton chain Add hydrogens Add R groups

17. 19-17 19.4 Primary Structure The primary structure of a protein is the amino acid sequence of the chain. Primary structures are translations of information contained in the genes.

18. 19-18 19.5 Secondary Structure The two very important secondary structures of proteins are:  -helix  -pleated sheet Both depend on hydrogen bonding between the amide H and the carbonyl O further down the chain or on a parallel chain.

19. 19-19  Helix Insert Fig 19.5 With caption

20. 19-20 B Sheet: Lewis Structure Parallel sheet Antiparallel sheet

21. 19-21 Types of Protein Structure 1 Fibrous proteins exist as long stranded molecules: Eg. Silk, collagen, wool. A colagen segment in space-filling mode illustrates this point. Red spheres represent oxygen, grey carbon, and blue nitrogen

22. 19-22 Types of Protein Structure 2 Globular proteins have somewhat spherical shapes. Most enzymes are globular. Eg. myoglobin, hemoglobin. Myoglobin in space- filling mode is the chosen example.

23. 19-23 19.6 Tertiary Structure The configuration of all the atoms in the protein chain: side chains prosthetic groups helical and pleated sheet regions

24. 19-24 Tertiary Structure: 2 Protein folding attractions: 1. Noncovalent forces a. Inter and intrachain H bonding b. Hydrophobic interactions c. Electrostatic attractions + to - ionic attraction d. Complexation with metal ions e. Ion-dipole 2. Covalent disulfide bridges

25. 19-25 Tertiary interactions: diag. ionic disulfide hydrophobic H bonds or dipole Ion-dipole metal coord’n

26. 19-26 19.7 Quaternary Structure Quaternary structure is the result of noncovalent interactions between two or more protein chains. In some cases the quaternary structure involves binding to a nonprotein group called a prosthetic group. Hemoglobin has four protein chains and the heme prosthetic group.

27. 19-27 19.8 Overview of Structure and Function The combination of 1 o, 2 o, 3 o, and 4 o structures lead to function. Some proteins are fibrous and have great strength. They make up the structural parts of cells. Some proteins are globular and serve as transport, regulatory and enzyme proteins.

28. 19-28 19.19 Myoglobin and Hemoglobin Hemoglobin transports oxygen to the cells while myoglobin stores oxygen in skeletal muscle. Both use the heme group to bind oxygen. Myoglobin has a single protein chain while hemoglobin has four (2 alpha and 2 beta). Each chain has a heme unit.

29. 19-29 The Heme Group Pyrrole ring N of His F8 binds to fifth site on the iron. His E7 acts as a ”gate” for oxygen.

30. 19-30 Myoglobin: 2 o and 3 o aspects Some helical regions Heme group with iron (orange) at the center

31. 19-31 Hemoglobin (Hb) Oxygen binds to heme in hemoglobin cooperatively: as one O 2 is bound, it becomes easier for the next to bind. The first oxygen causes 2,3-bisphospho- glycerate (BPG) to leave deoxyhemoglobin. This causes shape changes which favor more reaction with oxygen. H + produced by metabolizing cells (low pH) favors oxygen release from Hb and higher pH in the lungs favors binding of oxygen to Hb.

32. 19-32 Hemoglobin: ribbons + hemes Each chain is in ribbon form and color coded. The heme groups are in space filling form

33. 19-33 Oxygen Transport: Mother-Fetus Fetal Hb is different from maternal Hb. It does not bind BPG and therefore has a higher affinity for oxygen. This makes for more efficient oxygen transfer! Sickle cell hemoglobin (Hb S) has a valine substituted for a glutamic acid in the beta chain. This results in the deoxy version clumping and forming the characteristic sickle cells. People with the disease usually die young but those with only one copy of the gene (sickle cell trait) tend to resist maleria.

34. 19-34 19.10 Protein Denaturation Denaturing destroys the physiological function of the protein (remove the 2 o - 4 o interactions).. Heat (coagulation) Change in pH leads to coagulation or unfolding to to charge repulsion. Heavy metals Detergents Organic solvents

35. 19-35 19.11 Protein Digestion and Diet Digestion: Stomach: pepsin S. I.: trypsin, chymotrypsin, elastase, etc. Essential Amino Acids: Cannot be synthesized by humans Include: Ile, Leu, Lys, Met, Phe, Thr, Try, Val Complete protein from animals provides esential AA in proper proportions. Incomplete protein from vegetable sources must be balanced. E. g. beans (lys + trp) and corn (met)

36. 19-36 THE END Protein Structure And Function